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  • 251.
    Stenemo, M. Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala Univ, Dept Med Sci, Uppsala, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Proteomic profiling and the risk of heart failure2015In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 17, p. 141-141Article in journal (Other academic)
  • 252.
    Stenemo, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Molecular Epidemiology of Cardiovascular Disease2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cardiovascular disease is a major cause of morbidity and mortality, with increasing prevalence worldwide.

    Identification of risk markers may enable improved prevention by targeting high-risk individuals, earlier disease diagnosis and treatment, as well as stratification of disease subtypes with different treatment options, thereby minimizing side effects while increasing success rates.

    The overall aim of this thesis was to investigate associations between proteomic and metabolomic biomarkers, and the development of heart failure and ischemic stroke. Specific objectives were to examine potential causal pathways, and the added value in risk prediction of the identified risk markers.

    In Studies I–II, we performed proximity extension assay based proteomic profiling of ≥80 circulating proteins in the Swedish cohorts Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS n=901, median age 70), and the Uppsala Longitudinal Study of Adult Men (ULSAM, n=685, median age 77). In Study I, we identified nine proteins involved in apoptosis, inflammation, matrix remodeling, and fibrinolysis associated with incident heart failure, including growth differentiation factor-15 (GDF-15). In Study II, we identified several proteins associated with incident ischemic stroke, including GDF-15. Both studies revealed potential to improve disease risk prediction by using proteomic data.

    In Study III, we performed mass spectrometry-based metabolomic profiling in plasma or serum samples from PIVUS, ULSAM, and TwinGene (total n=3,924). The metabolites urobilin and sphingomyelin (30:1) were associated with incident heart failure.

    In Study IV, we followed up on the results of Studies I–II, performing Mendelian randomization analyses (a framework for causal analysis using genetic variants) in 1,053,527 individuals, with 88,448 coronary artery disease cases, 70,305 ischemic stroke cases, and 1,420 heart failure cases. This study supports a causal role of genetically elevated GDF-15 levels in heart failure development, but not in coronary artery disease or ischemic stroke.

    In conclusion, we identified multiple biomarkers associated with incident heart failure and ischemic stroke, potentially involved in early disease development. We also saw potential to improve disease risk prediction for incident heart failure and ischemic stroke using proteomics data.

    Our findings encourage further large-scale proteomic, metabolomic, and genetic studies to give new insights into heart failure and stroke pathogenesis.

  • 253.
    Stenemo, Markus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nowak, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford University School of Medicine, Department of Medicine, Division of Cardiovascular Medicine.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ärnlöv, Johan
    Dalarna University, School of Health and Social Studies, Falun; Karolinska Institutet, Care Science and Society, Department of Neurobiology, Division of Family Medicine and Primary Care .
    Circulating proteins as predictors of incident heart failure in the elderly2018In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 20, no 1, p. 55-62Article in journal (Refereed)
    Abstract [en]

    Aims

    To identify novel risk markers for incident heart failure using proteomic profiling of 80 proteins previously associated with cardiovascular pathology.

    Methods and results

    Proteomic profiling (proximity extension assay) was performed in two community‐based prospective cohorts of elderly individuals without heart failure at baseline: the Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS, n = 901, median age 70.2 (interquartile range 70.0–70.3) years, 80 events]; and the Uppsala Longitudinal Study of Adult Men [ULSAM, n = 685, median age 77.8 (interquartile range 76.9–78.1) years, 90 events]. Twenty‐nine proteins were associated with incident heart failure in the discovery cohort PIVUS after adjustment for age and sex, and correction for multiple testing. Eighteen associations replicated in ULSAM. In pooled analysis of both cohorts, higher levels of nine proteins were associated with incident heart failure after adjustment for established risk factors: growth differentiation factor 15 (GDF‐15), T‐cell immunoglobulin and mucin domain 1 (TIM‐1), tumour necrosis factor‐related apoptosis‐inducing ligand receptor 2 (TRAIL‐R2), spondin‐1 (SPON1), matrix metalloproteinase‐12 (MMP‐12), follistatin (FS), urokinase‐type plasminogen activator surface receptor (U‐PAR), osteoprotegerin (OPG), and suppression of tumorigenicity 2 (ST2). Of these, GDF‐15, U‐PAR, MMP‐12, TRAIL‐R2, SPON1 and FS were associated with worsened echocardiographic left ventricular systolic function at baseline, while only TIM‐1 was positively associated with worsened diastolic function (P < 0.02 for all).

    Conclusion

    Proteomic profiling identified several novel associations between proteins involved in apoptosis, inflammation, matrix remodelling, and fibrinolysis with incident heart failure in elderly individuals. Our results encourage additional studies investigating the underlying mechanisms and the clinical utility of our findings.

  • 254.
    Stojkovic, Stefan
    et al.
    Med Univ Vienna, Dept Internal Med 2, Vienna, Austria..
    Thulin, Åsa
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Hell, Lena
    Med Univ Vienna, Dept Internal Med 1, Clin Div Hematol & Hemostaseol, Vienna, Austria..
    Thaler, Barbara
    Med Univ Vienna, Dept Internal Med 2, Vienna, Austria..
    Rauscher, Sabine
    Med Univ Vienna, Core Facil, Vienna, Austria..
    Baumgartner, Johanna
    Med Univ Vienna, Dept Internal Med 2, Vienna, Austria..
    Groeger, Marion
    Med Univ Vienna, Core Facil, Vienna, Austria..
    Ay, Cihan
    Med Univ Vienna, Dept Internal Med 1, Clin Div Hematol & Hemostaseol, Vienna, Austria..
    Demyanets, Svitlana
    Med Univ Vienna, Dept Lab Med, Vienna, Austria..
    Neumayer, Christoph
    Med Univ Vienna, Dept Surg, Div Vasc Surg, Vienna, Austria..
    Huk, Ihor
    Med Univ Vienna, Dept Surg, Div Vasc Surg, Vienna, Austria..
    Spittler, Andreas
    Med Univ Vienna, Core Facil, Vienna, Austria.;Med Univ Vienna, Dept Surg, Div Vasc Surg, Vienna, Austria..
    Huber, Kurt
    Wilhelminen Hosp, Med Dept Cardiol & Emergency Med 3, Vienna, Austria.;Sigmund FReud Private Univ, Med Sch, Vienna, Austria..
    Wojta, Johann
    Med Univ Vienna, Dept Internal Med 2, Vienna, Austria.;Med Univ Vienna, Core Facil, Vienna, Austria.;Sigmund FReud Private Univ, Med Sch, Vienna, Austria.;Ludwig Boltzmann Cluster Cardiovascular Res, Vienna, Austria..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Åberg, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Science for Life Laboratory, SciLifeLab.
    IL-33 stimulates the release of procoagulant microvesicles from human monocytes and differentially increases tissue factor in human monocyte subsets2017In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 117, no 7, p. 1379-1390Article in journal (Refereed)
    Abstract [en]

    Monocytes and monocyte-derived microvesicles (MVs) are the main source of circulating tissue factor (TF). Increased monocyte TF expression and increased circulating levels of procoagulant MVs contribute to the formation of a prothrombotic state in patients with cardiovascular disease. Interleukin (IL)-33 is a pro-inflammatory cytokine involved in atherosclerosis and other inflammatory diseases, but its role in regulating thrombosis is still unclear. The aim of the present study was to investigate the effects of IL-33 on the procoagulant properties of human monocytes and monocyte-derived MVs. IL-33 induced a time- and concentration-dependent increase of monocyte TF mRNA and protein levels via binding to the ST2-receptor and activation of the NF-kappa B-pathway. The IL-33 treated monocytes also released CD14+TF+ MVs and IL-33 was found to increase the TF activity of both the isolated monocytes and monocyte-derived MVs. The monocytes were classified into subsets according to their CD14 and CD16 expression. Intermediate monocytes (IM) showed the highest ST2 receptor expression, followed by non-classical monocytes (NCM), and classical monocytes (CM). IL-33 induced a significant increase of TF only in the IM (p<0.01), with a tendency in NCM (p=0.06), but no increase was observed in CM. Finally, plasma levels of IL-33 were positively correlated with CD14+TF+ MVs in patients undergoing carotid endarterectomy (r=0.480; p=0.032; n=20). We hereby provide novel evidence that the proinflammatory cytokine IL-33 induces differential TF expression and activity in monocyte subsets, as well as the release of procoagulant MVs. In this manner, IL-33 may contribute to the formation of a prothrombotic state characteristic for cardiovascular disease.

  • 255. Strage, E. M.
    et al.
    Lewitt, M. S.
    Hanson, J. M.
    Olsson, U.
    Norrvik, F.
    Lilliehook, I.
    Holst, B. S.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Relationship among Insulin Resistance, Growth Hormone, and Insulin-Like Growth Factor I Concentrations in Diestrous Swedish Elkhounds2014In: Journal of Veterinary Internal Medicine, ISSN 0891-6640, E-ISSN 1939-1676, Vol. 28, no 2, p. 419-428Article in journal (Refereed)
    Abstract [en]

    Background In the dog, the normal estrous cycle includes a prolonged luteal phase. Progesterone stimulates local canine mammary growth hormone (GH) production, which may act systemically and contribute to insulin resistance. Swedish Elkhounds are predisposed to progesterone-related diabetes mellitus, and the relationship among insulin resistance, GH, and insulin-like growth factor I (IGF-I) is of particular interest. Objective To study insulin resistance in relation to GH and IGF-I in nondiabetic Swedish Elkhounds during diestrus. We also assessed whether alterations in these hormones could predict diestrus-linked diseases and all-cause mortality. Animals Eighty-four privately owned female intact Swedish Elkhounds >4years of age. Methods Blood sampling and clinical examination during luteal phase, with a follow-up questionnaire after 20months. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Results In multivariable regression analysis, GH was positively associated with HOMA-IR (P=.009). An increase in GH of 1ng/mL was associated with a 12.7% increase in HOMA-IR. Moreover, C-peptide was positively associated with IGF-I (P=.04), and an increase in C-peptide of 0.1ng/mL was associated with a 6.9% increase in IGF-I. Structural equation modeling supported these results. Twenty-three animals were found to have previously unrecognized mammary masses and had higher GH (P<.0001) and IGF-I (P=.007) than dogs without mammary masses (n=61). There was no association between high GH and IGF-I concentrations at sampling and future mammary masses. Conclusion We showed that GH was strongly associated with insulin resistance in older Swedish Elkhounds during diestrus.

  • 256. Strage, Emma M
    et al.
    Sundberg, Mårten
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Holst, Bodil S
    Andersson Franko, Mikael
    Ramström, Margareta
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Analytical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lewitt, Moira
    Effect of insulin treatment on circulating insulin-like growth factor I and IGF-binding proteins in cats with diabetes mellitus.2018In: Journal of Veterinary Internal Medicine, ISSN 0891-6640, E-ISSN 1939-1676, Vol. 32, no 5, p. 1579-1590Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Insulin-like growth factor-I (IGF-I) is used to screen for acromegaly in diabetic cats. In humans, most circulating IGF-I forms ternary complexes (TC) with IGF-binding protein (IGFBP-3) and an acid-labile subunit. Compared to humans, the amount of TC in cats is more variable. Insulin-like growth factor-I concentrations are reported to increase during insulin treatment, more rapidly in cats achieving remission.

    OBJECTIVES: To investigate (i) factors associated with circulating IGF-I concentrations, including IGFBP-profiles (ii) effect of insulin treatment on IGF-I concentrations and (iii) IGF-I as prognostic marker of diabetes mellitus remission.

    ANIMALS: Thirty-one privately owned diabetic cats of which 24 were followed 1 year, and 13 healthy cats.

    METHODS: Prospective study. Serum insulin, IGF-I, glucose, and fructosamine concentrations were measured. IGF-binding forms were determined by chromatography in 14 diabetic and 13 healthy cats; and IGF-I, IGF-II, IGFBP-3, and IGFBP-5 by mass spectrometry in 3 cats achieving remission.

    RESULTS: Insulin-like growth factor-I median (interquartile range) before start of insulin treatment was 300 (160-556) ng/mL. Insulin-like growth factor-I was positively associated with TC (P < .0001) and endogenous insulin (P = .005) and negatively associated with fructosamine (P < .0001). Median IGF-I was higher 2-4 weeks after start of insulin treatment compared with baseline (300 versus 670 ng/mL, P = .0001) and predicted future remission (P = .046). In cats that went into remission, the amount of TC and IGFBP-3 increased, suggesting increase in IGF-I is dependent on TC formation.

    CONCLUSIONS: Insulin treatment should be accounted for when interpreting IGF-I in diabetic cats. Insulin-like growth factor-I 2-4 weeks after initiation of insulin treatment shows promise as prognostic marker for remission in diabetic cats.

  • 257.
    Strawbridge, Rona J.
    et al.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Univ Glasgow, Inst Mental Hlth & Wellbeing, Mental Hlth & Wellbeing, Glasgow, Lanark, Scotland.;Univ Glasgow, Dept Hlth & Wellbeing, Glasgow G12 8RZ, Lanark, Scotland..
    Silveira, Angela
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    den Hoed, Marcel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England..
    Rybin, Denis
    Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.;Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA..
    Li-Gao, Ruifang
    Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands..
    Kavousi, Maryam
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Dehghan, Abbas
    Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England..
    Haljas, Kadri
    Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland..
    Lahti, Jari
    Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Gadin, Jesper R.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    Backlund, Alexandra
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    de Faire, Ulf
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Gertow, Karl
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    Giral, Phillipe
    Grp Hosp Pitie Salpetriere, AP HP, Serv Endocrinol Metab, Unites Prevent Cardiovasc, Paris, France..
    Goel, Anuj
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England..
    Humphries, Steve E.
    UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England..
    Kurl, Sudhir
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, Kuopio, Finland..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England.;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England.;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England..
    Lindgren, Cecilia C. M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Mannarino, Elmo
    Univ Perugia, Dept Clin & Expt Med Internal Med Angiol & Arteri, Perugia, Italy..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands..
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    de Mutsert, Renee
    Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Saliba-Gustafsson, Peter
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    Sennblad, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Evolution. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.
    Smit, Andries J.
    Univ Med Ctr Groningen, Dept Med, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Med, Groningen, Netherlands..
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Tremoli, Elena
    Univ Milan, Dipartimento Sci Farmacolog & Biomol, Milan, Italy.;IRCCS, Ctr Cardiolog Monzino, Milan, Italy..
    Veglia, Fabrizio
    IRCCS, Ctr Cardiolog Monzino, Milan, Italy..
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Bjorck, Hanna M.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden..
    Eriksson, Johan G.
    Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Hofman, Albert
    Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Franco, Oscar H.
    Watkins, Hugh
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands..
    Florez, Jose C.
    Massachusetts Gen Hosp, Diabet Unit, Boston, MA USA.;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA USA.;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Med, Cambridge, MA USA..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England..
    Meigs, James B.
    Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Med, Cambridge, MA USA.;Massachusetts Gen Hosp, Gen Med Div, Boston, MA USA..
    Ingelsson, Erik
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA USA..
    Baldassarre, Damiano
    Univ Milan, Dipartimento Sci Farmacolog & Biomol, Milan, Italy.;Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy..
    Hamsten, Anders
    Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation2017In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 266, p. 196-204Article in journal (Refereed)
    Abstract [en]

    Background and aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling.

    Methods: We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants.

    Results: We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures.

    Conclusions: We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT.

  • 258.
    Stubleski, Jordan
    et al.
    Örebro Univ, MTM Res Ctr, Sch Sci & Technol, Örebro, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Salihovic, Samira
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Örebro Univ, MTM Res Ctr, Sch Sci & Technol, Örebro, Sweden.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Kärrman, Anna
    Örebro Univ, MTM Res Ctr, Sch Sci & Technol, Örebro, Sweden.
    Longitudinal changes in persistent organic pollutants (POPs) from 2001 to 2009 in a sample of elderly Swedish men and women2018In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 165, p. 193-200Article in journal (Refereed)
    Abstract [en]

    Background: Prospective cohort studies evaluating the temporal trends of background-level persistent organic pollutants (POPs) and their potential negative health effects in humans are needed. Objective: The objectives of this study are to examine the five year longitudinal trend in chlorinated and bro-minated (Cl/Br) POP concentrations in a sample of elderly individuals and to investigate the relationship between gender, changes in body weight, plasma lipid levels and POP concentrations. Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, plasma samples were collected from the same individuals over a 5 year period. Originally 992 subjects (all aged 70) were sampled between 2001 and 2004 and 814 returning subjects (all aged 75) were sampled again from 2006 to 2009. Plasma concentrations of 16 polychlorinated biphenyls (PCBs), 5 organochlorine pesticides (OCPs), octachlorinated dibenzo-p-dioxin (OCDD), and one polybrominated diphenylether (BDE 47) were determined using high-throughput 96-well plate solid phase extraction and gas chromatography-high resolution mass spectrometry (GC-HAMS). Results: During the 5-year follow-up, plasma concentrations of all POPs significantly decreased (p < 0.00001). Median reductions ranged from 4% (PCB105) to 45% (PCB 99), with most reductions being in the 30-40% range. For most POPs, a larger decline was seen in men than in women. The relationship between the weight change and change in POP concentrations was generally negative, but a positive relationship between lipid levels and POP concentrations when expressed as wet-weight was observed. In general, similar changes in POP concentrations and their relationships to body weight were observed regardless of using either wet-weight (pg/ mL) or lipid-normalized (ng/g lipid) concentrations. Conclusion: In this longitudinal cohort study, gender and minor, but varying changes in body weight and lipid levels greatly influenced the individual-based changes in POP concentrations. In general, our findings suggest that men and women with larger decreases in body weight and greater increases in lipid levels have the slowest decline in body burden of POPs. Based on the results from this study, either wet-weight or lipid normalized concentrations can be used to determine the percent change in POP concentrations and their relationships to physiological changes and differences.

  • 259.
    Stubleski, Jordan
    et al.
    MTM Research Centre, School of Science and Technology, Örebro University, 70182 Örebro, Sweden.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    van Bavel, Bert
    MTM Research Centre, School of Science and Technology, Örebro University, 70182 Örebro, Sweden; Norwegian Institute for Water Research, NIVA, 0349 Oslo, Norway.
    Kärrman, Anna
    MTM Research Centre, School of Science and Technology, Örebro University, 70182 Örebro, Sweden.
    Changes in serum levels of perfluoroalkyl substances during a 10-year follow-up period in a large population-based cohort2016In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 95, p. 86-92Article in journal (Refereed)
    Abstract [en]

    Poly- and perfluoroalkyl substances (PFASs) are a group of man-made fluorinated chemicals which have, at background levels, been associated with negative health effects in humans. Thus far, most human biomonitoring studies have evaluated the general change in PFAS concentration over time by continuously testing various individuals. This is one of the few studies to report the longitudinal trend of a range of PFAS concentrations in humans. In addition, this is the first known longitudinal study to include a large background level exposed cohort of both men and women with the same age and location who were repeatedly sampled from 2001 to 2014. The longitudinal change in concentration of eight PFASs detected in serum collected from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort were determined and compared to results from general population studies. The sex-dependent changes in PFAS concentrations over time were also assessed. Serum was sampled from the same individuals at ages 70 (collection period 2001-2004), 75 (2006-2009) and 80 (2011-2014,). Eight (C6-11) of fourteen (C4-13) analyzed PFASs were usually detected in over 75% of individuals and assessed using a random effects (mixed) model. In the 579 individuals attending all three examinations, PFOSA and PFOS concentrations significantly decreased, while the remaining six PFASs significantly increased between ages 70 and 75. However, between ages 75 and 80 all PFAS concentrations significantly decreased. Overall from age 70 to 80, concentrations of PFHxS, PFUnDA, PFNA, and PFDA showed a significant increase (7% to 34%), whereas concentrations of PFOSA, PFHpA, PFOS, and PFOA (-75% to -27%) significantly decreased. Over time PFHxS concentrations increased more among women, while PFHpA concentrations showed a greater decrease among men. From age 70 to age 80, spanning from 2001-2004 to 2011-2014, the PIVUS cohort showed decreases in circulating levels of some PFASs phased out of production with the exception of PFHxS and C>8 PFASs. Contrary to other studies, PFHxS concentrations showed the greatest overall increase, which is likely attributed to a local drinking water contamination incident.

  • 260.
    Stubleski, Jordan
    et al.
    MTM Research Centre, School of Science and Technology, Örebro University, 70182 Örebro, Sweden.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Dunder, Linda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    McCleaf, Philip
    Uppsala Vatten och Avfall AB, Box 1105, 754 141 Uppsala.
    Eurén, Karin
    Uppsala Vatten och Avfall AB, Box 1105, 754 141 Uppsala.
    Ahrens, Lutz
    Swedish University of Agricultural Sciences (SLU), Department of Aquatic Sciences and Assessment, Gerda Nilssons väg 5, 756 51 Uppsala, Sweden.
    Svartengren, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    van Bavel, Bert
    MTM Research Centre, School of Science and Technology, Örebro University, 70182 Örebro, Sweden.; Norwegian Institute for Water Research, NIVA, 0349 Oslo, Norway.
    Kärrman, Anna
    MTM Research Centre, School of Science and Technology, Örebro University, 70182 Örebro, Sweden.
    The effect of drinking water contaminated with perfluoroalkyl substances on a 10-year longitudinal trend of plasma levels in an elderly Uppsala cohort2017In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 159, p. 95-102, article id S0013-9351(17)30897-6Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In 2012, drinking water contaminated with per- and polyfluoroalkyl substances (PFASs), foremost perfluorooctanesulfonic acid (PFOS) and perfluorohexanesulfonic acid (PFHxS) at levels over 20ng/L and 40ng/L, respectively, was confirmed in Uppsala, Sweden.

    OBJECTIVES: We assessed how a longitudinally sampled cohort's temporal trend in PFAS plasma concentration was influenced by their residential location and determined the plausible association or disparity between the PFASs detected in the drinking water and the trend in the study cohort.

    METHODS: The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort provided plasma samples three times from 2001 to 2014. Individuals maintaining the same zip code throughout the study (n = 399) were divided into a reference (no known PFAS exposure), low, intermediate and high exposure area depending on the proportion of contaminated drinking water received. Eight PFASs detected in the majority (75%) of the cohort's plasma samples were evaluated for significant changes in temporal PFAS concentrations using a random effects (mixed) model.

    RESULTS: PFHxS plasma concentrations continued to significantly increase in individuals living in areas receiving the largest percentage of contaminated drinking water (p < 0.0001), while PFOS showed an overall decrease. The temporal trend of other PFAS plasma concentrations did not show an association to the quality of drinking water received.

    CONCLUSIONS: The distribution of contaminated drinking water had a direct effect on the trend in PFHxS plasma levels among the different exposure groups, resulting in increased concentrations over time, especially in the intermediate and high exposure areas. PFOS and the remaining PFASs did not show the same relationship, suggesting other sources of exposure influenced these PFAS plasma trends.

  • 261. Surakka, Ida
    et al.
    Horikoshi, Momoko
    Magi, Reedik
    Sarin, Antti-Pekka
    Mahajan, Anubha
    Lagou, Vasiliki
    Marullo, Letizia
    Ferreira, Teresa
    Miraglio, Benjamin
    Timonen, Sanna
    Kettunen, Johannes
    Pirinen, Matti
    Karjalainen, Julia
    Thorleifsson, Gudmar
    Hägg, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hottenga, Jouke-Jan
    Isaacs, Aaron
    Ladenvall, Claes
    Beekman, Marian
    Esko, Tonu
    Ried, Janina S.
    Nelson, Christopher P.
    Willenborg, Christina
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Westra, Harm-Jan
    Blades, Matthew
    de Craen, Anton J. M.
    de Geus, Eco J.
    Deelen, Joris
    Grallert, Harald
    Hamsten, Anders
    Havulinna, Aki S.
    Hengstenberg, Christian
    Houwing-Duistermaat, Jeanine J.
    Hypponen, Elina
    Karssen, Lennart C.
    Lehtimaki, Terho
    Lyssenko, Valeriya
    Magnusson, Patrik K. E.
    Mihailov, Evelin
    Muller-Nurasyid, Martina
    Mpindi, John-Patrick
    Pedersen, Nancy L.
    Penninx, Brenda W. J. H.
    Perola, Markus
    Pers, Tune H.
    Peters, Annette
    Rung, Johan
    Smit, Johannes H.
    Steinthorsdottir, Valgerdur
    Tobin, Martin D.
    Tsernikova, Natalia
    van Leeuwen, Elisabeth M.
    Viikari, Jorma S.
    Willems, Sara M.
    Willemsen, Gonneke
    Schunkert, Heribert
    Erdmann, Jeanette
    Samani, Nilesh J.
    Kaprio, Jaakko
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Gieger, Christian
    Metspalu, Andres
    Slagboom, P. Eline
    Groop, Leif
    van Duijn, Cornelia M.
    Eriksson, Johan G.
    Jula, Antti
    Salomaa, Veikko
    Boomsma, Dorret I.
    Power, Christine
    Raitakari, Olli T.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jarvelin, Marjo-Riitta
    Thorsteinsdottir, Unnur
    Franke, Lude
    Ikonen, Elina
    Kallioniemi, Olli
    Pietiainen, Vilja
    Lindgren, Cecilia M.
    Stefansson, Kari
    Palotie, Aarno
    McCarthy, Mark I.
    Morris, Andrew P.
    Prokopenko, Inga
    Ripatti, Samuli
    The impact of low-frequency and rare variants on lipid levels2015In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, no 6, p. 589-597Article in journal (Refereed)
    Abstract [en]

    Using a genome-wide screen of 9.6 million genetic variants achieved through 1000 Genomes Project imputation in 62,166 samples, we identify association to lipid traits in 93 loci, including 79 previously identified loci with new lead SNPs and 10 new loci, 15 loci with a low-frequency lead SNP and 10 loci with a missense lead SNP, and 2 loci with an accumulation of rare variants. In six loci, SNPs with established function in lipid genetics (CELSR2, GCKR, LIPC and APOE) or candidate missense mutations with predicted damaging function (CD300LG and TM6SF2) explained the locus associations. The low-frequency variants increased the proportion of variance explained, particularly for low-density lipoprotein cholesterol and total cholesterol. Altogether, our results highlight the impact of low-frequency variants in complex traits and show that imputation offers a cost-effective alternative to resequencing.

  • 262.
    Surendran, Praveen
    et al.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Drenos, Fotios
    Univ Bristol, Sch Social & Community Med, Med Res Council Integrat Epidemiol Unit, Oakfield House, Bristol, Avon, England.;UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England..
    Young, Robin
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Warren, Helen
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England..
    Cook, James P.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Manning, Alisa K.
    Harvard Med Sch, Dept Genet, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Sim, Xueling
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Biostat, Ann Arbor, MI USA.;Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Barnes, Daniel R.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Witkowska, Kate
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England..
    Staley, James R.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Tragante, Vinicius
    Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands..
    Tukiainen, Taru
    Harvard Med Sch, Dept Genet, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA..
    Yaghootkar, Hanieh
    Univ Exeter, Inst Biomed & Clin Sci, Genet Complex Traits, Sch Med, Exeter, Devon, England..
    Masca, Nicholas
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Natl Inst Hlth, Res Leicester Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England..
    Freitag, Daniel F.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Ferreira, Teresa
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Giannakopoulou, Olga
    Queen Mary Univ London, William Harvey Res Inst, Bads & London Sch Med & Dent, Ctr Heart, London, England..
    Tinker, Andrew
    Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England.;Queen Mary Univ London, William Harvey Res Inst, Bads & London Sch Med & Dent, Ctr Heart, London, England..
    Harakalova, Magdalena
    Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Liu, Chunyu
    NHLBI, Framingham, MA USA.;Boston Univ, Framingham Heart Study, Framingham, MA USA..
    Kraja, Aldi T.
    Washington Univ, Ctr Genome Sci & Syst Biol, Div Stat Genom, Sch Med, St Louis, MO USA.;Washington Univ, Dept Genet, Sch Med, St Louis, MO USA..
    Nielsen, Sune Fallgaard
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev Hosp, Herlev, Denmark..
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Samue, Maria
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Zhao, Wei
    Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Bonnycastle, Lori L.
    NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Jackson, Anne U.
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Biostat, Ann Arbor, MI USA..
    Narisu, Narisu
    NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Swift, Amy J.
    NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Southam, Lorraine
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England..
    Marten, Jonathan
    Univ Edinburgh, Med Res Council Human Genet Unit, Med Res Council Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Huyghe, Jeroen R.
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Biostat, Ann Arbor, MI USA..
    Stancakova, Alena
    Univ Eastern Finland, Dept Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Fava, Cristiano
    Lund Univ, Dept Clin Sci, Malmo, Sweden.;Univ Verona, Dept Med, Verona, Italy..
    Ohlsson, Therese
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Matchan, Angela
    Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England..
    Stirrups, Kathleen E.
    Queen Mary Univ London, William Harvey Res Inst, Bads & London Sch Med & Dent, Ctr Heart, London, England.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Gjesing, Anette P.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Kontto, Jukka
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Perola, Markus
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med FIMM, Helsinki, Finland..
    Shaw-Hawkins, Susan
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England..
    Havulinna, Aki S.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Zhang, He
    Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA..
    Donnelly, Louise A.
    Univ Dundee, Med Res Inst, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Groves, Christopher J.
    Univ Oxford, Radcliffe Dept Med, Ctr Diabet, Endocrinol & Metab, Oxford, England..
    Rayner, N. William
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England.;Univ Oxford, Radcliffe Dept Med, Ctr Diabet, Endocrinol & Metab, Oxford, England..
    Neville, Matt J.
    Univ Oxford, Radcliffe Dept Med, Ctr Diabet, Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trusts, Natl Inst Hlth, Res Oxford Biomed Res Ctr, Oxford, England..
    Robertson, Neil R.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Ctr Diabet, Endocrinol & Metab, Oxford, England..
    Yiorkas, Andrianos M.
    Imperial Coll London, Sect Invest Med, London, England.;Brunel Univ London, Dept Life Sci, London, England..
    Herzig, Karl-Heinz
    Univ Oulu, Inst Biomed, Bioctr Oulu, Oulu, Finland.;Poznan Univ Med Sci, Dept Gastroenterol & Metab, Poznan, Poland..
    Kajantie, Eero
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Hosp Children & Adolescents, Helsinki, Finland.;Univ Helsinki, Helsinki, Finland.;Oulu Univ Hosp, Dept Obstet & Gynaecol, Oulu, Finland.;Univ Oulu, Oulu, Finland..
    Zhang, Weihua
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Gen Hosp, Dept Cardiol, Middlesex, Middx, England..
    Willems, Sara M.
    Univ Cambridge, Sch Clin Med, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Malerba, Giovanni
    Univ Verona, Dept Neurosci Biomed & Movement Sci, Sect Biol & Genet, Verona, Italy..
    Soranzo, Nicole
    Univ Cambridge, Dept Haematol, Cambridge, England.;Wellcome Trust Sanger Inst, Human Genet, Hinxton, England.;Univ Cambridge, NIHR Blbod & Transplant Res Unit Donor Hlth & Gen, Cambridge, England..
    Trabetti, Elisabetta
    Univ Verona, Dept Neurosci Biomed & Movement Sci, Sect Biol & Genet, Verona, Italy..
    Verweij, Niek
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    Evangelou, Evangelos
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Univ Ioannina, Dept Hyg & Epidemiol, Sch Med, Ioannina, Greece..
    Moayyeri, Alireza
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;UCL, Farr Inst Hlth Informat Res, Inst Hlth Informat, London, England..
    Vergnaud, Anne-Claire
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England..
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Natl Inst Hlth, Res Leicester Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England..
    Poveda, Alaitz
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Univ Basque Country UPV EHU, Fac Sci & Technol, Dept Genet Phys Anthropol & Anim Physiol, Bilbao, Spain..
    Varga, Tibor V.
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden..
    Caslake, Muriel
    Univ Glasgow, Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    de Craen, Anton J. M.
    Leiden Univ, Dept Gerontol & Geriatr, Med Ctr, Leiden, Netherlands..
    Trompet, Stella
    Leiden Univ, Dept Gerontol & Geriatr, Med Ctr, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Scott, Robert A.
    Univ Cambridge, Sch Clin Med, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Harris, Sarah E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Med Res Council Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland..
    Liewald, David C. M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Marioni, Riccardo
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Med Res Council Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Menni, Cristina
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Farmaki, Aliki-Eleni
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Hallmans, Goran
    Umea Univ, Dept Biobank Res, Umea, Sweden..
    Renstrom, Frida
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Umea Univ, Dept Biobank Res, Umea, Sweden..
    Huffman, Jennifer E.
    NHLBI, Framingham, MA USA.;Boston Univ, Framingham Heart Study, Framingham, MA USA.;Univ Edinburgh, Med Res Council Human Genet Unit, Med Res Council Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Hassinen, Maija
    Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Burgess, Stephen
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Vasan, Ramachandran S.
    NHLBI, Framingham, MA USA.;Boston Univ, Framingham Heart Study, Framingham, MA USA.;Boston Univ, Dept Med, Sect Cardiol, Sch Med, Boston, MA USA.;Boston Univ, Sch Publ Hlth, Boston, MA USA.;Boston Univ, Dept Med, Sect Prevent Med, Sch Med, Boston, MA USA.;Boston Univ, Dept Med, Sect Epidemiol, Sch Med, Boston, MA USA.;Boston Univ, Sch Publ Hlth, Boston, MA USA..
    Felix, Janine F.
    Erasmus MC, Univ Med Ctr Rotterdam, Dept Epidemiol, Rotterdam, Netherlands..
    Uria-Nickelsen, Maria
    Pfizer Worldwide Res & Dev, Dev Management & Planning, Cambridge, MA USA..
    Malarstign, Anders
    Pfizer Worldwide Res & Dev, Stockholm, Sweden..
    Reilly, Dermot F.
    Merck Res Labs, Genet & Pharmacogen, Boston, MA USA..
    Hoek, Maarten
    Merck Res Labs, Cardiometab Dis, Kenilworth, NJ USA..
    Vogt, Thomas F.
    Merck Res Labs, Cardiometab Dis, Kenilworth, NJ USA.;CHDI Management CHDI Fdn, Princeton, NJ USA..
    Lin, Honghuang
    NHLBI, Framingham, MA USA.;Boston Univ, Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02215 USA..
    Lieb, Wolfgang
    Univ Kiel, Inst Epidemiol & Biobank Popgen, Kiel, Germany..
    Traylor, Matthew
    Univ Cambridge, Neurol Unit, Cambridge Biomed Campus, Cambridge, England..
    Markus, Hugh S.
    Univ Cambridge, Neurol Unit, Cambridge Biomed Campus, Cambridge, England..
    Highland, Heather M.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Justice, Anne E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Marouli, Eirini
    Queen Mary Univ London, William Harvey Res Inst, Bads & London Sch Med & Dent, Ctr Heart, London, England..
    Lindstrom, Jaana
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Uusitupa, Matti
    Univ Eastern Finland, Dept Publ Hlth & Clin Nutr, Kuopio, Finland.;Kuopio Univ Hosp, Res Unit, Kuopio, Finland..
    Komulainen, Pirjo
    Kuopio Res Inst Exercise Med, Kuopio, Finland..
    Lakka, Timo A.
    Kuopio Res Inst Exercise Med, Kuopio, Finland.;Univ Eastern Finland, Inst Biomed Physiol, Kuopio Campus, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Polasek, Ozren
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.;Univ Split, Fac Med, Split, Croatia..
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Franks, Paul W.
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA..
    Dedoussis, George
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Jousilahti, Pekka
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Mannisto, Satu
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Wareham, Nick J.
    Univ Cambridge, Sch Clin Med, Med Res Council Epidemiol Unit, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Brown, Morris J.
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England..
    Dominiczak, Anna F.
    Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Connell, John M.
    Univ Dundee, Med Res Inst, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands..
    Sattar, Naveed
    Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Ford, Ian
    Univ Glasgow, Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Packard, Chris J.
    Univ Glasgow, Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Esko, Tonu
    Harvard Med Sch, Dept Genet, Boston, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Boston Childrens Hosp, Div Endocrinol, Boston, MA USA..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Inst Mol & Cell Biol, Tartu, Estonia..
    de Boer, Rudolf A.
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    van der Meer, Peter
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands..
    Gambaro, Giovanni
    Catholic Univ, Columbus Gemelli Univ Hosp, Dept Internal Med & Med Speciales, Div Nephrol, Rome, Italy..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Dept Epidemiol, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Numans, Mattijs E.
    Univ Med Ctr Utrecht, Dept Epidemiol, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Leiden Univ, Dept Publ Hlth & Primary Care, Med Ctr, Leiden, Netherlands.;Imperial Coll Healthcare NHS Trust, London, England..
    Brandslund, Ivan
    Lillebaelt Hosp, Dept Clin Biochem, Vejle, Denmark.;Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark..
    Christensen, Cramer
    Lillebaelt Hosp, Dept Med, Vejle, Denmark..
    Petersen, Eva R. B.
    Lillebaelt Hosp, Dept Clin Immunol & Biochem, Vejle, Denmark..
    Korpi-Hyovalti, Eeva
    South Ostrobothnia Cent Hosp, Dept Internal Med, Seinajoki, Finland..
    Oksa, Heikki
    Tampere Univ Hosp, Dept Internal Med, Tampere, Finland..
    Chambers, John C.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Gen Hosp, Dept Cardiol, Middlesex, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Kooner, Jaspal S.
    Ealing Gen Hosp, Dept Cardiol, Middlesex, Middx, England.;Imperial Coll London, Natl Heart & Lung Inst, London, England..
    Blakemore, Alexandra I. F.
    Imperial Coll London, Sect Invest Med, London, England.;Brunel Univ London, Dept Life Sci, London, England..
    Franks, Steve
    Imperial Coll London, Inst Reprod & Dev Biol, London, England..
    Jarvelin, Marjo-Riitta
    Imperial Coll London, Dept Epidemiol & Biostat, Med Res Council Publ Hlth England Ctr Environm &, Sch Publ Hlth,Fac Med, St Marys Campus, London, England.;Univ Oulu, Ctr Life Course Hlth Res, Fac Med, Oulu, Finland.;Univ Oulu, Bioctr Oulu, Oulu, Finland.;Oulu Univ Hosp, Unit Primary Care, Oulu, Finland..
    Husemoen, Lise L.
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark..
    Linneberg, Allan
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark.;Glostrup Univ Hosp, Dept Clin Expt Res, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Skaaby, Tea
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark..
    Thuesen, Betina
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark..
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Ctr Diabet, Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trusts, Natl Inst Hlth, Res Oxford Biomed Res Ctr, Oxford, England..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Dasman Diabet Inst, Kuwait, Kuwait.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia..
    Doney, Alex S. F.
    Univ Dundee, Med Res Inst, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Morris, Andrew D.
    Univ Edinburgh, Sch Med, Sch Mol Genet & Populat Hlth Sci, Teviot Pl, Edinburgh, Midlothian, Scotland..
    Palmer, Colin N. A.
    Univ Dundee, Med Res Inst, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Holmen, Oddgeir Lingaas
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway.;Univ Trondheim Hosp, St Olav Hosp, Trondheim, Norway..
    Hveem, Kristian
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway.;Nord Trondelag Hlth Trust, Levanger Hosp, Dept Med, Levanger, Norway..
    Willer, Cristen J.
    Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Tuomi, Tiinamaija
    Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Dept Endocrinol, Cent Hosp, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland..
    Groop, Leif
    Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Lund Univ, Dept Clin Sci Diabet & Endocrinol, Ctr Diabet, Malmo, Sweden..
    Karajamaki, AnneMari
    Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland.;Vaasa Hlth Care Ctr, Ctr Diabet, Vaasa, Finland..
    Palotie, Aarno
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Massachusetts Gen Hosp, Dept Psychiat, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA..
    Ripatti, Samuli
    Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Alam, Dewan S.
    ICDDR, Dhaka, Bangladesh..
    Majmnder, Abdulla Al Shafi
    Natl Inst Cardiovasc Dis, Dhaka, Bangladesh..
    Di Angelantonio, Emanuele
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, NIHR Blbod & Transplant Res Unit Donor Hlth & Gen, Cambridge, England..
    Chowdhury, Rajiv
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    McCarthy, Mark I.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Ctr Diabet, Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trusts, Natl Inst Hlth, Res Oxford Biomed Res Ctr, Oxford, England..
    Poulter, Neil
    Imperial Coll London, Sch Publ Hlth, London, England..
    Stanton, Alice V.
    Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin, Ireland..
    Sever, Peter
    Imperial Coll London, Natl Heart & Lung Inst, London, England..
    Amouyel, Philippe
    Univ Lille, UMR 1167, Risk Factors & Mol Determinants Aging Related Dis, Lille, France.;INSERM, Lille, France.;CHU Lille, Publ Hlth, Lille, France.;Inst Pasteur, Lille, France..
    Arveiler, Dominique
    Univ Strasbourg, Dept Epidemiol & Publ Hlth, EA 3430, Strasbourg, France..
    Blankenberg, Stefan
    Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany.;Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany..
    Ferrieres, Jean
    Toulouse Univ, Dept Epidemiol, UMR 1027, INSERM,CHU Toulouse, Toulouse, France..
    Kee, Frank
    Queens Univ, UKCRC Ctr Excellence Publ Hlth, Belfast, Antrim, North Ireland..
    Kuulasmaa, Kari
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Muller-Nurasyid, Martina
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Veronesi, Giovanni
    Univ Insubria, Dept Clin & Expt Med, Res Ctr Epidemiol & Prevent Med, Varese, Italy..
    Virtamo, Jarmo
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Bads & London Sch Med & Dent, Ctr Heart, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Elliott, Paul
    Imperial Coll London, Dept Epidemiol & Biostat, Med Res Council Publ Hlth England Ctr Environm &, Sch Publ Hlth,Fac Med, St Marys Campus, London, England..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Genome Campus, Hinxton, England..
    Kathiresan, Sekar
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA..
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden..
    Kuusisto, Johanna
    Univ Eastern Finland, Dept Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Laakso, Markku
    Univ Eastern Finland, Dept Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Padmanabhan, Sandosh
    Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Porteous, David J.
    Univ Edinburgh, Med Res Council Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland..
    Hayward, Caroline
    Univ Edinburgh, Med Res Council Human Genet Unit, Med Res Council Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Scotland, Generation
    Collaborat Univ Med Sch & NHS, Aberdeen, Scotland.;Collaborat Univ Med Sch & NHS, Dundee, Scotland.;Collaborat Univ Med Sch & NHS, Edinburgh, Midlothian, Scotland.;Collaborat Univ Med Sch & NHS, Glasgow, Lanark, Scotland..
    Collins, Francis S.
    NHGRI, Med Genom & Metab Genet Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Boehnke, Michael
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Biostat, Ann Arbor, MI USA..
    Stringham, Heather M.
    Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Biostat, Ann Arbor, MI USA..
    Frossard, Philippe
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Newton-Cheh, Christopher
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Tobin, Martin D.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Nordestgaard, Borge Gronne
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev Hosp, Herlev, Denmark..
    Caulfield, Mark J.
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England..
    Mahajan, Anubha
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Tomaszewski, Maciej
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Natl Inst Hlth, Res Leicester Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England.;Univ Manchester, Div Cardiovasc Sci, Manchester, Lancs, England..
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Natl Inst Hlth, Res Leicester Biomed Res Unit Cardiovasc Dis, Leicester, Leics, England..
    Saleheen, Danish
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.;Ctr Noncommunicable Dis, Karachi, Pakistan.;Univ Penn, Dept Biostat & Epidemiol, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;UCL, Inst Cardiovasc Sci, Fac Populat Hlth Sci, London, England..
    Lindgren, Cecilia M.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England..
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, NIHR Blbod & Transplant Res Unit Donor Hlth & Gen, Cambridge, England.;Wellcome Trust Sanger Inst, Hinxton, England..
    Wain, Louise V.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.;Univ Cambridge, NIHR Blbod & Transplant Res Unit Donor Hlth & Gen, Cambridge, England..
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England..
    Munroe, Patricia B.
    Queen Mary Univ London, William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England.;Wellcome Trust Sanger Inst, Hinxton, England..
    Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension2016In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 48, no 10, p. 1151-1161Article in journal (Refereed)
    Abstract [en]

    High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low frequency and common genetic variants in up to 192,763 individuals and used similar to 155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.

  • 263. Swaminathan, Bhairavi
    et al.
    Thorleifsson, Guomar
    Joud, Magnus
    Ali, Mina
    Johnsson, Ellinor
    Ajore, Ram
    Sulem, Patrick
    Halvarsson, Britt-Marie
    Eyjolfsson, Guomundur
    Haraldsdottir, Vilhelmina
    Hultman, Christina
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Kristinsson, Sigurour Y.
    Kahler, Anna K.
    Lenhoff, Stig
    Masson, Gisli
    Mellqvist, Ulf-Henrik
    Mansson, Robert
    Nelander, Sven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Neuro-Oncology.
    Olafsson, Isleifur
    Siguroardottir, Olof
    Steingrimsdottir, Hlif
    Vangsted, Annette
    Vogel, Ulla
    Waage, Anders
    Nahi, Hareth
    Gudbjartsson, Daniel F.
    Rafnar, Thorunn
    Turesson, Ingemar
    Gullberg, Urban
    Stefansson, Kari
    Hansson, Markus
    Thorsteinsdottir, Unnur
    Nilsson, Bjorn
    Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma2015In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, article id 7213Article in journal (Refereed)
    Abstract [en]

    Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR) = 1.25; P = 9.6 x 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells. We find that the MM risk allele harbours a Thr298Ala missense variant in an ELL2 domain required for transcription elongation. Consistent with a hypomorphic effect, we find that the MM risk allele also associates with reduced levels of immunoglobulin A (IgA) and G (IgG) in healthy subjects (P = 8.6 x 10(-9) and P = 6.4 x 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR = 1.30; P = 0.0024).

  • 264. Tang, Wenbo
    et al.
    Kowgier, Matthew
    Loth, Daan W.
    Artigas, Maria Soler
    Joubert, Bonnie R.
    Hodge, Emily
    Gharib, Sina A.
    Smith, Albert V.
    Ruczinski, Ingo
    Gudnason, Vilmundur
    Mathias, Rasika A.
    Harris, Tamara B.
    Hansel, Nadia N.
    Launer, Lenore J.
    Barnes, Kathleen C.
    Hansen, Joyanna G.
    Albrecht, Eva
    Aldrich, Melinda C.
    Allerhand, Michael
    Barr, R. Graham
    Brusselle, Guy G.
    Couper, David J.
    Curjuric, Ivan
    Davies, Gail
    Deary, Ian J.
    Dupuis, Josee
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Foy, Millennia
    Franceschini, Nora
    Gao, Wei
    Glaeser, Sven
    Gu, Xiangjun
    Hancock, Dana B.
    Heinrich, Joachim
    Hofman, Albert
    Imboden, Medea
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    James, Alan
    Karrasch, Stefan
    Koch, Beate
    Kritchevsky, Stephen B.
    Kumar, Ashish
    Lahousse, Lies
    Li, Guo
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, Cecilia
    Liu, Yongmei
    Lohman, Kurt
    Lumley, Thomas
    McArdle, Wendy L.
    Meibohm, Bernd
    Morris, Andrew P.
    Morrison, Alanna C.
    Musk, Bill
    North, Kari E.
    Palmer, Lyle J.
    Probst-Hensch, Nicole M.
    Psaty, Bruce M.
    Rivadeneira, Fernando
    Rotter, Jerome I.
    Schulz, Holger
    Smith, Lewis J.
    Sood, Akshay
    Starr, John M.
    Strachan, David P.
    Teumer, Alexander
    Uitterlinden, Andre G.
    Voelzke, Henry
    Voorman, Arend
    Wain, Louise V.
    Wells, Martin T.
    Wilk, Jemma B.
    Williams, O. Dale
    Heckbert, Susan R.
    Stricker, Bruno H.
    London, Stephanie J.
    Fornage, Myriam
    Tobin, Martin D.
    O'Connor, George T.
    Hall, Ian P.
    Cassano, Patricia A.
    Large-Scale Genome-Wide Association Studies and Meta-Analyses of Longitudinal Change in Adult Lung Function2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 7, p. e100776-Article in journal (Refereed)
    Abstract [en]

    Background: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. Methods: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. Results: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P = 5.71 x 10(-7)). In addition, meta-analysis using the five cohorts with >= 3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P = 2.18 x 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. Conclusions: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

  • 265. Thrift, Aaron P.
    et al.
    Gong, Jian
    Peters, Ulrike
    Chang-Claude, Jenny
    Rudolph, Anja
    Slattery, Martha L.
    Chan, Andrew T.
    Esko, Tonu
    Wood, Andrew R.
    Yang, Jian
    Vedantam, Sailaja
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Pers, Tune H.
    Baron, John A.
    Bezieau, Stephane
    Kuery, Sebastien
    Ogino, Shuji
    Berndt, Sonja I.
    Casey, Graham
    Haile, Robert W.
    Du, Mengmeng
    Harrison, Tabitha A.
    Thornquist, Mark
    Duggan, David J.
    Le Marchand, Loic
    Lemire, Mathieu
    Lindor, Noralane M.
    Seminara, Daniela
    Song, Mingyang
    Thibodeau, Stephen N.
    Cotterchio, Michelle
    Win, Aung Ko
    Jenkins, Mark A.
    Hopper, John L.
    Ulrich, Cornelia M.
    Potter, John D.
    Newcomb, Polly A.
    Schoen, Robert E.
    Hoffmeister, Michael
    Brenner, Hermann
    White, Emily
    Hsu, Li
    Campbell, Peter T.
    Mendelian randomization study of height and risk of colorectal cancer2015In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 44, no 2, p. 662-672Article in journal (Refereed)
    Abstract [en]

    Background: For men and women, taller height is associated with increased risk of all cancers combined. For colorectal cancer (CRC), it is unclear whether the differential association of height by sex is real or is due to confounding or bias inherent in observational studies. We performed a Mendelian randomization study to examine the association between height and CRC risk. Methods: To minimize confounding and bias, we derived a weighted genetic risk score predicting height (using 696 genetic variants associated with height) in 10 226 CRC cases and 10 286 controls. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for associations between height, genetically predicted height and CRC. Results: Using conventional methods, increased height (per 10-cm increment) was associated with increased CRC risk (OR = 1.08, 95% CI = 1.02-1.15). In sex-specific analyses, height was associated with CRC risk for women (OR = 1.15, 95% CI = 1.05-1.26), but not men (OR = 0.98, 95% CI = 0.92-1.05). Consistent with these results, carrying greater numbers of (weighted) height-increasing alleles (per 1-unit increase) was associated with higher CRC risk for women and men combined (OR = 1.07, 95% CI = 1.01-1.14) and for women (OR = 1.09, 95% CI = 1.01-1.19). There was weaker evidence of an association for men (OR = 1.05, 95% CI = 0.96-1.15). Conclusion: We provide evidence for a causal association between height and CRC for women. The CRC-height association for men remains unclear and warrants further investigation in other large studies.

  • 266.
    Tikkanen, Emmi
    et al.
    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Amar, David
    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Shcherbina, Anna
    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Waggott, Daryl
    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Ashley, Euan A.
    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Ingelsson, Erik
    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 6451Article in journal (Refereed)
    Abstract [en]

    We performed a large genome-wide association study to discover genetic variation associated with muscular strength, and to evaluate shared genetic aetiology with and causal effects of muscular strength on several health indicators. In our discovery analysis of 223,315 individuals, we identified 101 loci associated with grip strength (P <5 x 10(-8)). Of these, 64 were associated (P < 0.01 and consistent direction) also in the replication dataset (N=111,610). eQTL analyses highlighted several genes known to play a role in neuro-developmental disorders or brain function, and the results from meta-analysis showed a significant enrichment of gene expression of brain-related transcripts. Further, we observed inverse genetic correlations of grip strength with cardiometabolic traits, and positive correlation with parents' age of death and education. We also showed that grip strength had shared biological pathways with indicators of frailty, including cognitive performance scores. By use of Mendelian randomization, we provide evidence that higher grip strength is protective of both coronary heart disease (OR= 0.69, 95% CI 0.60-0.79, P < 0.0001) and atrial fibrillation (OR = 0.75, 95% CI 0.62-0.90, P = 0.003). In conclusion, our results show shared genetic aetiology between grip strength, and cardiometabolic and cognitive health; and suggest that maintaining muscular strength could prevent future cardiovascular events.

  • 267.
    Tikkanen, Emmi
    et al.
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ingelsson, Erik
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Associations of Fitness, Physical Activity, Strength, and Genetic Risk With Cardiovascular Disease Longitudinal Analyses in the UK Biobank Study2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 137, no 24, p. 2583-2591Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Observational studies have shown inverse associations among fitness, physical activity, and cardiovascular disease. However, little is known about these associations in individuals with elevated genetic susceptibility for these diseases.

    METHODS: We estimated associations of grip strength, objective and subjective physical activity, and cardiorespiratory fitness with cardiovascular events and all-cause death in a large cohort of 502635 individuals from the UK Biobank (median follow-up, 6.1 years; interquartile range, 5.4-6.8 years). Then we further examined these associations in individuals with different genetic burden by stratifying individuals based on their genetic risk scores for coronary heart disease and atrial fibrillation. We compared disease risk among individuals in different tertiles of fitness, physical activity, and genetic risk using lowest tertiles as reference.

    RESULTS: Grip strength, physical activity, and cardiorespiratory fitness showed inverse associations with incident cardiovascular events (coronary heart disease: hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.77-0.81; HR, 0.95; 95% CI, 0.93-0.97; and HR, 0.68; 95% CI, 0.63-0.74, per SD change, respectively; atrial fibrillation: HR, 0.75; 95% CI, 0.73-0.76; HR, 0.93; 95% CI, 0.91-0.95; and HR, 0.60; 95% CI, 0.56-0.65, per SD change, respectively). Higher grip strength and cardiorespiratory fitness were associated with lower risk of incident coronary heart disease and atrial fibrillation in each genetic risk score group (P-trend <0.001 in each genetic risk category). In particular, high levels of cardiorespiratory fitness were associated with 49% lower risk for coronary heart disease (HR, 0.51; 95% CI, 0.38-0.69) and 60% lower risk for atrial fibrillation (HR, 0.40; 95%, CI 0.30-0.55) among individuals at high genetic risk for these diseases.

    CONCLUSIONS: Fitness and physical activity demonstrated inverse associations with incident cardiovascular disease in the general population, as well as in individuals with elevated genetic risk for these diseases.

  • 268.
    Trombley, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Rocha, A.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology. CSIC, IATS, Torre Sal S-N, Ribera De Cabanes 12595, Castellon, Spain..
    Björnsson, B. Th.
    Univ Gothenburg, Dept Biol & Environm Sci, SE-40530 Gothenburg, Sweden..
    Borg, B.
    Univ Stockholm, Dept Zool, S-10691 Stockholm, Sweden..
    Schmitz, Monika
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Effects of androgens on the leptin system in immature male Atlantic salmon parr2018In: General and Comparative Endocrinology, ISSN 0016-6480, E-ISSN 1095-6840, Vol. 257, p. 122-129Article in journal (Refereed)
    Abstract [en]

    Leptin modulates all levels of the reproductive endocrine axis in mammals, and in turn, both leptin and the leptin receptor are regulated by sex steroids. The aim of this study was to investigate if sex steroids regulate the leptin system also in fish. Immature one-year old male Atlantic salmon parr were implanted with Silclear capsules that were either empty or filled with 11-ketoandrostenedione (11 KA) or testosterone (T) and the effects of 35-days treatment were investigated on measures of maturation, gene expression of leptin (lepa1, lepa2), leptin receptor (lepra1) and circulating plasma leptin. Both 11-KA and T stimulated the reproductive axis by increasing testes weight and up-regulated pituitary lh-beta mRNA levels and for T also fsh-beta. T up-regulated transcription levels of lepa1 and lepra1 in the pituitary, while 11-KA had no effect. Leptin receptor expression in the testis was unaltered by either androgen. T up-regulated lepa1 mRNA levels significantly also in the liver, but had no effect on lepa2, and 11 KA did not affect hepatic gene expression of either lepa1 or lepa2. Plasma leptin levels did not differ significantly between treatments. The results indicate that androgens regulate gene expression of leptin and the leptin receptor in different tissues in fish and that the effects of leptin might be tissue specific considering plasma levels remained unaltered. Overall, the results suggest a role for leptin in fish reproduction, where sex steroids are able to regulate components of the leptin system differentially in liver and important tissues of the reproductive axis.

  • 269.
    Turcot, Valerie
    et al.
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada..
    Lu, Yingchang
    Vanderbilt Univ, Sch Med, Div Epidemiol, Dept Med,Vanderbilt Ingram Canc Ctr,Vanderbilt Ep, Nashville, TN 37212 USA.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Highland, Heather M.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.;Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Univ Texas Sch Publ Hlth, Univ Texas MD Anderson Canc Ctr,UTHealth Grad Sch, Houston, TX 77030 USA..
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Justice, Anne E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Fine, Rebecca S.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA..
    Bradfield, Jonathan P.
    Childrens Hosp Philadelphia, Div Human Genet, Ctr Appl Gen, Philadelphia, PA 19104 USA.;Quantinuum Res LLC, San Diego, CA USA..
    Esko, Tonu
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Giri, Ayush
    Vanderbilt Univ, Dept Med, Div Epidemiol, Inst Med & Publ Hlth,Vanderbilt Genet Inst, Nashville, TN USA..
    Graff, Mariaelisa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Guo, Xiuqing
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Hendricks, Audrey E.
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Colorado, Dept Math & Stat Sci, Denver, CO 80202 USA..
    Karaderi, Tugce
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Eastern Mediterranean Univ, Fac Arts & Sci, Dept Biol Sci, Gazimagusa, Cyprus..
    Lempradl, Adelheid
    Max Planck Inst Immunobiol & Epigenet, Freiburg, Germany..
    Locke, Adam E.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO USA..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Marouli, Eirini
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England..
    Sivapalaratnam, Suthesh
    AMC, Dept Vasc Med, Amsterdam, Netherlands.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Young, Kristin L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Alfred, Tamuno
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Gen, St Louis, MO 63110 USA..
    Masca, Nicholas G. D.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Manning, Alisa K.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA USA..
    Medina-Gomez, Carolina
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Mudgal, Poorva
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA..
    Reiner, Alex P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Vedantam, Sailaja
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA..
    Willems, Sara M.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Winkler, Thomas W.
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Aben, Katja K.
    Netherlands Comprehens Canc Org, Utrecht, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Alam, Dewan S.
    York Univ, Sch Kinesiol & Hlth Sci, Fac Hlth, Toronto, ON, Canada..
    Alharthi, Sameer E.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Allison, Matthew
    Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA..
    Amouyel, Philippe
    INSERM, U1167, Lille, France.;Inst Pasteur, U1167, Lille, France.;Univ Lille, U1167, RID AGE Risk Factors & Mol Determinants Aging Rel, Lille, France..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England..
    Auer, Paul L.
    Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA..
    Balkau, Beverley
    Ctr Rech Epidemiol & Sante Populat CESP, U1018, INSERM, Villejuif, France..
    Bang, Lia E.
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Cambridge, Metabol Res Labs, Cambridge, England.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Wellcome Trust MRC Inst Metab Sci, Cambridge, England..
    Bastarache, Lisa
    Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Benn, Marianne
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark..
    Bergmann, Sven
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland.;Swiss Inst Bioinformat, Lausanne, Switzerland..
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Blueher, Matthias
    Univ Leipzig, IFB Adipos Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbrucke DIfE, Dept Epidemiol, Nuthetal, Germany..
    Boerwinkle, Eric
    Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Univ Texas Sch Publ Hlth, Univ Texas MD Anderson Canc Ctr,UTHealth Grad Sch, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Boeger, Carsten A.
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Bots, Michiel L.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Brandslund, Ivan
    Lillebaelt Hosp, Dept Clin Biochem, Vejle, Denmark.;Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark..
    Breen, Gerome
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London, England.;South London & Maudsley Hosp, NIHR Biomed Res Ctr Mental Hlth, London, England..
    Brilliant, Murray H.
    Marshfield Clin Res Inst, Marshfield, WI USA..
    Broer, Linda
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Brumat, Marco
    Univ Trieste, Dept Med Sci, Trieste, Italy..
    Burt, Amber A.
    Univ Washington, Dept Med, Seattle, WA USA..
    Butterworth, Adam S.
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England..
    Campbell, Peter T.
    Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA..
    Cappellani, Stefania
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Carey, David J.
    Geisinger Hlth Syst, Weis Ctr Res, Danville, PA USA..
    Catamo, Eulalia
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Caulfield, Mark J.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London, England..
    Chambers, John C.
    Ealing Gen Hosp, London North West Healthcare NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Chasman, Daniel I.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Chen, Yii-Der I.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Chowdhury, Rajiv
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England..
    Christensen, Cramer
    Lillebaelt Hosp, Med Dept, Vejle, Denmark..
    Chu, Audrey Y.
    NHLBI Framingham Heart Study, Framingham, MA USA.;Merck Sharp & Dohme Ltd, Genet & Pharmacogen, Boston, MA USA..
    Cocca, Massimiliano
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Collins, Francis S.
    NHGRI, US Natl Inst Hlth, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Corley, Janie
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Galbany, Jordi Corominas
    Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Human Genet, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Ophthalmol, Nijmegen, Netherlands..
    Cox, Amanda J.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA.;Griffith Univ, Menzies Hlth Inst Queensland, Southport, Qld, Australia..
    Crosslin, David S.
    Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98195 USA..
    Cuellar-Partida, Gabriel
    Univ Queensland, Diamantina Inst, Brisbane, Qld, Australia.;QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    D'Eustacchio, Angela
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Danesh, John
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Dept Med, British Heart Fdn Cambridge Ctr Excellence, Cambridge, England..
    Davies, Gail
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Ctr Mol Med, Dept Genet, Utrecht, Netherlands..
    Groot, Mark C. H.
    Univ Med Ctr Utrecht, Div Lab & Pharm, Dept Clin Chem & Haematol, Utrecht, Netherlands.;Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, Utrecht, Netherlands..
    Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Dedoussis, George
    Harokopio Univ, Dept Nutr & Dietet, Sch Hlth Sci & Educ, Athens, Greece..
    Demerath, Ellen W.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Heijer, Martin
    Vrije Univ Amsterdam Med Ctr, Dept Internal Med, Amsterdam, Netherlands..
    Hollander, Anneke I.
    Radboud Univ Nijmegen, Med Ctr, Donders Inst Brain Cognit & Behav, Dept Ophthalmol, Nijmegen, Netherlands..
    Ruijter, Hester M.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Utrecht, Netherlands..
    Dennis, Joe G.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England..
    Denny, Josh C.
    Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Angelantonio, Emanuele
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England..
    Drenos, Fotios
    UCL, Inst Cardiovasc Sci, London, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Du, Mengmeng
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.;Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA..
    Dube, Marie-Pierre
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.;Univ Montreal, Dept Med, Fac Med, Montreal, PQ, Canada..
    Dunning, Alison M.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England..
    Easton, Douglas F.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.;Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England..
    Edwards, Todd L.
    Vanderbilt Univ, Dept Med, Div Epidemiol, Inst Med & Publ Hlth,Vanderbilt Genet Inst, Nashville, TN USA..
    Ellinghaus, David
    Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany..
    Ellinor, Patrick T.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA USA..
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England..
    Evangelou, Evangelos
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina, Greece..
    Farmaki, Aliki-Eleni
    Harokopio Univ, Dept Nutr & Dietet, Sch Hlth Sci & Educ, Athens, Greece.;Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Farooqi, I. Sadaf
    Univ Cambridge, Metabol Res Labs, Cambridge, England.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Wellcome Trust MRC Inst Metab Sci, Cambridge, England..
    Faul, Jessica D.
    Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA..
    Fauser, Sascha
    Univ Cologne, Dept Ophthalmol, Cologne, Germany..
    Feng, Shuang
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Ferrannini, Ele
    CNR, Inst Clin Physiol, Pisa, Italy.;Univ Pisa, Dept Clin & Expt Med, Pisa, Italy..
    Ferrieres, Jean
    Toulouse Univ, Sch Med, Toulouse, France..
    Florez, Jose C.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA USA..
    Ford, Ian
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Franke, Andre
    Christian Albrechts Univ Kiel, Inst Clin Mol Biol, Kiel, Germany..
    Franks, Paul W.
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.;Umea Univ, Med Unit, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Friedrich, Nele
    Univ Med Greifswald, Inst Clin Chem, Greifswald, Germany.;Univ Med Greifswald, Lab Med, Greifswald, Germany..
    Frikke-Schmidt, Ruth
    Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark..
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Gan, Wei
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Gandin, Ilaria
    AREA Sci Pk, Res Unit, Trieste, Italy..
    Gasparini, Paolo
    Univ Trieste, Dept Med Sci, Trieste, Italy.;IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Gibson, Jane
    Univ Southampton, Fac Nat & Environm Sci, Ctr Biol Sci, Southampton, Hants, England..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gjesing, Anette P.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Gordon-Larsen, Penny
    Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.;Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC USA..
    Gorski, Mathias
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany.;Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany..
    Grabe, Hans-Joergen
    Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany.;German Ctr Neurodegenerat Dis DZNE, Greifswald, Germany..
    Grant, Struan F. A.
    Childrens Hosp Philadelphia, Div Human Genet, Ctr Appl Gen, Philadelphia, PA 19104 USA.;Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.;Childrens Hosp Philadelphia, Div Endocrinol, Philadelphia, PA 19104 USA..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Griffiths, Helen L.
    Univ Southampton, Fac Med, Clin Neurosci Res Grp, Vis Sci, Southampton, Hants, England..
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Sch Publ Hlth, Houston, TX 77030 USA..
    Gudnason, Vilmundur
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Iceland Heart Assoc, Kopavogur, Iceland..
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Haessler, Jeff
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Hakonarson, Hakon
    Childrens Hosp Philadelphia, Div Human Genet, Ctr Appl Gen, Philadelphia, PA 19104 USA.;Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Hammerschlag, Anke R.
    Vrije Univ Amsterdam, Dept Complex Trait Genet, Ctr Neurogen & Cognit Res, Amsterdam Neurosci, Amsterdam, Netherlands..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Harris, Kathleen Mullan
    Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA.;Univ N Carolina, Dept Sociol, Chapel Hill, NC USA..
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, US Natl Inst Hlth, Bethesda, MD 20892 USA..
    Hattersley, Andrew T.
    Univ Exeter, Med Sch, Exeter, Devon, England..
    Have, Christian T.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    He, Liang
    Duke Univ, Social Sci Res Inst, Biodemog Aging Res Unit, Durham, NC USA.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Heard-Costa, Nancy L.
    NHLBI Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA..
    Heath, Andrew C.
    Washington Univ, Dept Psychiat, St Louis, MO USA..
    Heid, Iris M.
    Univ Regensburg, Dept Genet Epidemiol, Regensburg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany..
    Helgeland, Oyvind
    Haukeland Hosp, Dept Pediat, Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway..
    Hernesniemi, Jussi
    Tampere Univ Hosp, Ctr Heart, Dept Cardiol, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Tampere, Finland.;Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland..
    Hewitt, Alex W.
    Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.;Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Vis Sci, Perth, WA, Australia.;Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas, Australia..
    Holmen, Oddgeir L.
    Norwegian Univ Sci & Technol, NTNU, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, Trondheim, Norway..
    Hovingh, G. Kees
    AMC, Dept Vasc Med, Amsterdam, Netherlands..
    Howson, Joanna M. M.
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England..
    Hu, Yao
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Huang, Paul L.
    Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Huffman, Jennifer E.
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Neurol, Rotterdam, Netherlands.;Erasmus MC, Dept Radiol, Rotterdam, Netherlands..
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Jansson, Jan-Hakan
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Res Unit Skelleftea, Skelleftea, Sweden..
    Jarvik, Gail P.
    Univ Washington, Dept Med, Seattle, WA USA.;Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA..
    Jensen, Gorm B.
    Frederiksberg Univ Hosp, Copenhagen City Heart Study, Frederiksberg, Denmark..
    Jia, Yucheng
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Johansson, Stefan
    Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway.;Haukeland Hosp, Ctr Med Genet & Mol Med, Bergen, Norway..
    Jorgensen, Marit E.
    Univ Southern Denmark, Natl Inst Publ Hlth, Copenhagen, Denmark.;Steno Diabet Ctr Copenhagen, Gentofte, Denmark..
    Jorgensen, Torben
    Vanderbilt Univ, Dept Biomed Informat, 221 Kirkland Hall, Nashville, TN 37235 USA.;Aalborg Univ, Fac Med, Aalborg, Denmark.;Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Interunivers Cardiol Inst Netherlands, Utrecht, Netherlands..
    Kahali, Bratati
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA.;Indian Inst Sci, Ctr Brain Res, Bangalore, Karnataka, India..
    Kahn, Rene S.
    Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands..
    Kahonen, Mika
    Univ Tampere, Fac Med & Life Sci, Dept Clin Physiol, Tampere, Finland.;Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland..
    Kamstrup, Pia R.
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark..
    Kanoni, Stavroula
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England..
    Kaprio, Jaakko
    Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland..
    Karaleftheri, Maria
    Echinos Med Ctr, Echinos, Greece..
    Kardia, Sharon L. R.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Karpe, Fredrik
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Kathiresan, Sekar
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA..
    Kee, Frank
    Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth Res, Belfast, Antrim, North Ireland..
    Kiemeney, Lambertus A.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Kim, Eric
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Kitajima, Hidetoshi
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Komulainen, Pirjo
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.;Univ Eastern Finland, Sch Med, Inst Biomed, Kuopio Campus, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Kooner, Jaspal S.
    Ealing Gen Hosp, London North West Healthcare NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll London, Natl Heart & Lung Inst, Hammersmith Hosp Campus, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA..
    Korhonen, Tellervo
    Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland..
    Kovacs, Peter
    Univ Leipzig, IFB Adipos Dis, Leipzig, Germany..
    Kuivaniemi, Helena
    Geisinger Hlth Syst, Weis Ctr Res, Danville, PA USA.;Stellenbosch Univ, Fac Med & Hlth Sci, Dept Psychiat, Tygerberg, South Africa.;Stellenbosch Univ, Fac Med & Hlth Sci, Dept Biomed Sci, Div Mol Biol & Human Genet, Tygerberg, South Africa..
    Kutalik, Zoltan
    Swiss Inst Bioinformat, Lausanne, Switzerland.;Lausanne Univ Hosp, Inst Social & Prevent Med, Lausanne, Switzerland..
    Kuulasmaa, Kari
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Lakka, Timo A.
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.;Univ Eastern Finland, Sch Med, Inst Biomed, Kuopio Campus, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland..
    Lamparter, David
    Univ Lausanne, Dept Computat Biol, Lausanne, Switzerland.;Swiss Inst Bioinformat, Lausanne, Switzerland..
    Lange, Ethan M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Lange, Leslie A.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Larson, Eric B.
    Univ Washington, Dept Med, Seattle, WA USA.;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA..
    Lee, Nanette R.
    Univ San Carlos, Dept Anthropol Sociol & Hist, Cebu, Philippines.;Univ San Carlos, USC Off Populat Studies Fdn Inc, Cebu, Philippines..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland..
    Lewis, Cora E.
    Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL USA..
    Li, Huaixing
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Li, Jin
    Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA..
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Lin, Honghuang
    Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA..
    Lin, Keng-Hung
    Taichung Vet Gen Hosp, Dept Ophthalmol, Taichung, Taiwan..
    Lin, Li-An
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Lin, Xu
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindstrom, Jaana
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Linneberg, Allan
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark.;Rigshosp, Dept Clin Expt Res, Copenhagen, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Liu, Dajiang J.
    Penn State Univ, Coll Med, Inst Personalized Med, Dept Publ Hlth Sci, Hershey, PA USA..
    Liu, Yongmei
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA..
    Lo, Ken S.
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada..
    Lophatananon, Artitaya
    Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry, W Midlands, England..
    Lotery, Andrew J.
    Univ Southampton, Fac Med, Clin Neurosci Res Grp, Vis Sci, Southampton, Hants, England..
    Loukola, Anu
    Univ Helsinki, Dept Publ Hlth, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Lubitz, Steven A.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland..
    Mannisto, Satu
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Marenne, Gaelle
    Wellcome Trust Sanger Inst, Hinxton, England..
    Mazul, Angela L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    McKean-Cowdin, Roberta
    Univ Southern Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA..
    Medland, Sarah E.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Meidtner, Karina
    German Inst Human Nutr Potsdam Rehbrucke DIfE, Dept Mol Epidemiol, Nuthetal, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Mistry, Vanisha
    Univ Cambridge, Metabol Res Labs, Cambridge, England.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Wellcome Trust MRC Inst Metab Sci, Cambridge, England..
    Mitchell, Paul
    Univ Sydney, Ctr Vis Res, Westmead Millennium Inst Med Res, Sydney, NSW, Australia.;Univ Sydney, Dept Ophthalmol, Sydney, NSW, Australia..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Moilanen, Leena
    Kuopio Univ Hosp, Dept Med, Kuopio, Finland..
    Moitry, Marie
    Univ Strasbourg, Dept Epidemiol & Publ Hlth, Strasbourg, France.;Univ Hosp Strasbourg, Dept Publ Hlth, Strasbourg, France..
    Montgomery, Grant W.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands..
    Moore, Carmel
    Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Cambridge, Dept Publ Hlth & Primary Care, INTERVAL Coordinating Ctr, Cambridge, England..
    Mori, Trevor A.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA, Australia..
    Morris, Andrew D.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med, Munich, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany..
    Munroe, Patricia B.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London, England..
    Nalls, Mike A.
    NIA, Lab Neurogenet, US Natl Inst Hlth, Bethesda, MD 20892 USA.;Data Tecn Int, Glen Echo, MD USA..
    Narisu, Narisu
    NHGRI, US Natl Inst Hlth, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Nelson, Christopher P.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Nielsen, Sune F.
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark..
    Nikus, Kjell
    Tampere Univ Hosp, Ctr Heart, Dept Cardiol, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Tampere, Finland..
    Njolstad, Pal R.
    Haukeland Hosp, Dept Pediat, Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway..
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark..
    Nyholt, Dale R.
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.;Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld, Australia..
    O'Connel, Jeffrey R.
    Univ Maryland, Sch Med, Program Personalized & Genom Med, Dept Med, Baltimore, MD 21201 USA..
    O'Donoghue, Michelle L.
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Loohuis, Loes M. Olde
    Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA..
    Ophoff, Roel A.
    Univ Med Ctr Utrecht, Dept Psychiat, Brain Ctr Rudolf Magnus, Utrecht, Netherlands.;Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA..
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Packard, Chris J.
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Padmanabhan, Sandosh
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Palmer, Colin N. A.
    Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Med Res Inst, Dundee, Scotland..
    Palmer, Nicholette D.
    Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA..
    Pasterkamp, Gerard
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, Utrecht, Netherlands..
    Patel, Aniruddh P.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA..
    Pattie, Alison
    Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark..
    Peissig, Peggy L.
    Marshfield Clin Res Inst, Marshfield, WI USA..
    Peloso, Gina M.
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Pennell, Craig E.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA, Australia..
    Perola, Markus
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, Helsinki, Finland..
    Perry, James A.
    Univ Maryland, Sch Med, Program Personalized & Genom Med, Dept Med, Baltimore, MD 21201 USA..
    Perry, John R. B.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Pers, Tune H.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark..
    Person, Thomas N.
    Marshfield Clin Res Inst, Marshfield, WI USA..
    Peters, Annette
    German Ctr Diabet Res, Neuherberg, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Neuherberg, Germany..
    Petersen, Eva R. B.
    Lillebaelt Hosp, Dept Clin Immunol & Biochem, Vejle, Denmark..
    Peyser, Patricia A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Pirie, Ailith
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England..
    Polasek, Ozren
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.;Univ Split, Sch Med, Split, Croatia..
    Polderman, Tinca J.
    Vrije Univ Amsterdam, Dept Complex Trait Genet, Ctr Neurogen & Cognit Res, Amsterdam Neurosci, Amsterdam, Netherlands..
    Puolijoki, Hannu
    Cent Hosp Southern Ostrobothnia, Seinajoki, Finland..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland..
    Rasheed, Asif
    Ctr Noncommun Dis, Karachi, Pakistan..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.;Univ Eastern Finland, Sch Med, Inst Biomed, Kuopio Campus, Kuopio, Finland..
    Reilly, Dermot F.
    Merck Sharp & Dohme Ltd, Genet & Pharmacogen, Boston, MA USA..
    Renstrom, Frida
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden.;Umea Univ, Dept Biobank Res, Umea, Sweden..
    Rheinberger, Myriam
    Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany..
    Ridker, Paul M.
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Rioux, John D.
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.;Univ Montreal, Dept Med, Fac Med, Montreal, PQ, Canada..
    Rivas, Manuel A.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Univ Oxford, Nuffield Dept Clin Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Roberts, David J.
    Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Dept Publ Hlth & Primary Care, Cambridge, England.;NHS Blood & Transplant Oxford Ctr, Oxford, England.;Univ Oxford, BRC Haematol Theme & Radcliffe Dept Med, Oxford, England..
    Robertson, Neil R.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Robino, Antonietta
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.;Umea Univ, Unit Family Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Ruth, Katherine S.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Saleheen, Danish
    Ctr Noncommun Dis, Karachi, Pakistan.;Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA USA..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland..
    Samani, Nilesh J.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Sapkota, Yadav
    QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia..
    Sattar, Naveed
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Schoen, Robert E.
    Univ Pittsburgh, Dept Med, Med Ctr, Pittsburgh, PA USA.;Univ Pittsburgh, Med Ctr, Dept Epidemiol, Pittsburgh, PA USA..
    Schreiner, Pamela J.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Schulze, Matthias B.
    German Inst Human Nutr Potsdam Rehbrucke DIfE, Dept Mol Epidemiol, Nuthetal, Germany.;German Ctr Diabet Res, Neuherberg, Germany..
    Scott, Robert A.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Segura-Lepe, Marcelo P.
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Shah, Svati H.
    Duke Univ, Duke Mol Physiol Inst, Durham, NC USA..
    Sheu, Wayne H. -H.
    Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrinol & Metab, Taichung, Taiwan.;Natl Def Med Ctr, Sch Med, Taipei, Taiwan.;Natl Yang Ming Univ, Sch Med, Taipei, Taiwan..
    Sim, Xueling
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.;Natl Univ Singapore, Natl Univ Hlth Syst, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Slater, Andrew J.
    GlaxoSmithKline, Genet, Target Sci, Res Triangle Pk, NC USA.;OmicSoft Qiagen Co, Cary, NC USA..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Smith, Albert V.
    Univ Iceland, Fac Med, Reykjavik, Iceland.;Iceland Heart Assoc, Kopavogur, Iceland..
    Southam, Lorraine
    Wellcome Trust Sanger Inst, Hinxton, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Speliotes, Elizabeth K.
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland..
    Stefansson, Kari
    Univ Iceland, Fac Med, Reykjavik, Iceland..
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen E.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Strauch, Konstantin
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany.;Amgen Inc, deCODE Genet, Reykjavik, Iceland.;Ludwig Maximilians Univ Munchen, Fac Med, IBE, Chair Genet Epidemiol, Munich, Germany..
    Stringham, Heather M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Stumvoll, Michael
    Univ Leipzig, IFB Adipos Dis, Leipzig, Germany.;Univ Leipzig, Dept Med, Leipzig, Germany..
    Sun, Liang
    Duke Univ, Social Sci Res Inst, Biodemog Aging Res Unit, Durham, NC USA.;Univ Helsinki, Dept Publ Hlth, Helsinki, Finland..
    Surendran, Praveen
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England..
    Swift, Amy J.
    NHGRI, US Natl Inst Hlth, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Tada, Hayato
    Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA.;Kanazawa Univ, Kanazawa, Ishikawa, Japan..
    Tansey, Katherine E.
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England.;Cardiff Univ, Coll Biomed & Life Sci, Cardiff, S Glam, Wales..
    Tardif, Jean-Claude
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada..
    Taylor, Kent D.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Thompson, Deborah J.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England..
    Thorleifsson, Gudmar
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, Reykjavik, Iceland..
    Thuesen, Betina H.
    Capital Reg Denmark, Res Ctr Prevent & Hlth, Glostrup, Denmark..
    Toenjes, Anke
    Univ Leipzig, Dept Womens & Child Hlth, Ctr Pediat Res, Leipzig, Germany..
    Tromp, Gerard
    Geisinger Hlth Syst, Weis Ctr Res, Danville, PA USA.;Stellenbosch Univ, Fac Med & Hlth Sci, Dept Biomed Sci, Div Mol Biol & Human Genet, Tygerberg, South Africa..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Tsafantakis, Emmanouil
    Anogia Med Ctr, Anogia, Greece..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;Dasman Diabet Inst, Dasman, Kuwait.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia..
    Tybjaerg-Hansen, Anne
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark..
    Tyrer, Jonathan P.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England..
    Uher, Rudolf
    Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Uusitupa, Matti
    Univ Eastern Finland, Dept Publ Hlth & Clin Nutr, Kuopio, Finland..
    Laan, Sander W.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Utrecht, Netherlands..
    Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Leeuwen, Nienke
    Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands.;Leiden Univ, Med Ctr, Dept Mol Cell Biol, Leiden, Netherlands..
    van Setten, Jessica
    Univ Med Ctr Utrecht, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands..
    Vanhala, Mauno
    Cent Hosp Cent Finland, Primary Hlth Care Unit, Jyvaskyla, Finland.;Kuopio Univ Hosp, Primary Hlth Care Unit, Kuopio, Finland..
    Varbo, Anette
    Copenhagen Univ Hosp, Dept Clin Biochem, Herlev & Gentofte Hosp, Herlev, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark..
    Varga, Tibor V.
    Lund Univ, Genet & Mol Epidemiol Unit, Dept Clin Sci, Malmo, Sweden..
    Varma, Rohit
    Univ Southern Calif, Dept Ophthalmol, Keck Sch Med, USC Roski Eye Inst, Los Angeles, CA USA..
    Edwards, Digna R. Velez
    Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Genet Inst, Dept Obstet & Gynecol, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Vermeulen, Sita H.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Veronesi, Giovanni
    Univ Insubria, Dept Med & Surg, Res Ctr Epidemiol & Prevent Med, Varese, Italy..
    Vestergaard, Henrik
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Steno Diabet Ctr Copenhagen, Gentofte, Denmark..
    Vitart, Veronique
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Vogt, Thomas F.
    Merck Sharp & Dohme Ltd, Cardiometabol Dis, Kenilworth, NJ USA..
    Voelker, Uwe
    German Ctr Cardiovasc Res DZHK, Partner Site Greifswald, Greifswald, Germany.;Univ Med Greifswald, Interfaculty Inst Genet & Funct Gen, Greifswald, Germany..
    Vuckovic, Dragana
    Univ Trieste, Dept Med Sci, Trieste, Italy.;IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Wagenknecht, Lynne E.
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA..
    Walker, Mark
    Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle, NSW, Australia..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wang, Feijie
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Wang, Carol A.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA, Australia..
    Wang, Shuai
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Wang, Yiqin
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Ware, Erin B.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.;Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Warren, Helen R.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London, England..
    Waterworth, Dawn M.
    GlaxoSmithKline, Target Sci, Genet, King Of Prussia, PA USA..
    Wessel, Jennifer
    Indiana Univ, Dept Epidemiol, Fairbanks Sch Publ Hlth, Diabet Translat Res Ctr, Indianapolis, IN 46204 USA.;Indiana Univ, Dept Med, Fairbanks Sch Publ Hlth, Diabet Translat Res Ctr, Indianapolis, IN 46204 USA.;Indiana Univ, Sch Med, Indianapolis, IN USA..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    Willer, Cristen J.
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Witte, Daniel R.
    Danish Diabet Acad, Odense, Denmark.;Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark..
    Wood, Andrew R.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Wu, Ying
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Yaghootkar, Hanieh
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Yao, Jie
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Yao, Pang
    Univ Chinese Acad Sci, Chinese Acad Sci, Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China..
    Yerges-Armstrong, Laura M.
    Univ Maryland, Sch Med, Program Personalized & Genom Med, Dept Med, Baltimore, MD 21201 USA.;GlaxoSmithKline, King Of Prussia, PA USA..
    Young, Robin
    Univ Cambridge, MRC BHF Cardiovasc Epidemiol Unit, Dept Publ Hlth & Primary Care, Cambridge, England.;Univ Glasgow, Glasgow, Lanark, Scotland..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Hinxton, England..
    Zhan, Xiaowei
    Univ Texas Southwestern Med Ctr Dallas, Dept Clin Sci, Quantitat Biomed Res Ctr, Ctr Genet Host Def, Dallas, TX 75390 USA..
    Zhang, Weihua
    Ealing Gen Hosp, London North West Healthcare NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Zhao, Wei
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.;Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA USA..
    Zhou, Wei
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Zondervan, Krina T.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Nuffield Dept Obstet & Gynaecol, Endometriosis CaRe Ctr, Oxford, England..
    Rotter, Jerome I.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Pospisilik, John A.
    Max Planck Inst Immunobiol & Epigenet, Freiburg, Germany..
    Rivadeneira, Fernando
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, Div Stat Gen, St Louis, MO 63110 USA..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England..
    Lettre, Guillaume
    Univ Montreal, Montreal Heart Inst, Montreal, PQ, Canada.;Univ Montreal, Dept Med, Fac Med, Montreal, PQ, Canada..
    North, Kari E.
    Dept Epidemiol, Chapel Hill, NC USA.;Carolina Ctr Genome Sci, Chapel Hill, NC USA..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England..
    Hirschhorn, Joel N.
    Broad Inst & MIT Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Dept Genet, Boston, MA 02115 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.;Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA..
    Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity2018In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 1, p. 26-+Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

  • 270. Ueda, Peter
    et al.
    Cnattingius, Sven
    Stephansson, Olof
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ludvigsson, Jonas F.
    Bonamy, Anna-Karin Edstedt
    Cerebrovascular and ischemic heart disease in young adults born preterm: a population-based Swedish cohort study2014In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 29, no 4, p. 253-260Article in journal (Refereed)
    Abstract [en]

    Preterm birth is associated with overall cardiovascular mortality in young adulthood, but which specific conditions that underlie this association is unknown. We studied mortality and morbidity from cerebrovascular and ischemic heart disease in individuals born preterm. In a nationwide Swedish study, we included 1,306,943 individuals without congenital malformations born between 1983 and 1995, followed from 15 years of age to December 31st, 2010. Of these, 73,489 (5.6 %) were born preterm (< 37 weeks of gestation). Cox proportional hazards regression analysis was used to calculate hazard ratios (HR) with 95 % confidence intervals (CI), after adjusting for maternal characteristics and birth weight for gestational age. Of 955 incident cases of cerebrovascular disease, 58 (6.1 %) occurred in preterm born subjects. The corresponding numbers of ischemic heart disease cases were 180 and 13 (7.2 %), respectively. Birth before 32 weeks was associated with a nearly twofold increased risk of cerebrovascular disease; adjusted HR, (95 % CI) = 1.89 (1.01-3.54) compared to term born individuals, whereas individuals born at 32-36 weeks were not at increased risk. Preterm birth was not associated with later ischemic heart disease; no cases of ischemic heart disease were recorded among those born before 32 weeks and the HR (95 % CI) for those born at 32-36 weeks of gestation was 1.45 (0.81-2.57), compared to term-born individuals. Birth before 32 weeks is associated with increased risk of cerebrovascular disease in young adulthood. Our data suggest that cardiovascular health promotion in follow-up programs after very preterm birth may be beneficial.

  • 271.
    van der Laan, Sander W.
    et al.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Soumare, Aicha
    Univ Bordeaux, INSERM, U1219, Team Vintage, Bordeaux, France..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany.;German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany..
    Sedaghat, Sanaz
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Baumert, Jens
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Zabaneh, Delilah
    UCL, Dept Genet Environm & Evolut, London, England.;UCL, Genet Inst, London, England..
    van Setten, Jessica
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Isgum, Ivana
    Univ Med Ctr Utrecht, Image Sci Inst, Utrecht, Netherlands..
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Arpegard, Johannes
    Karolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    Amouyel, Philippe
    Univ Lille, INSERM, Lille, France.;Inst Pasteur, Lille, France..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol P C5, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Waldenberger, Melanie
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Doerr, Marcus
    German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany..
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Felix, Janine F.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Morrison, Alanna C.
    Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA..
    Franceschini, Nora
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA..
    Kavousi, Maryam
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    O'Donnell, Christopher
    Boston Vet Adm Healthcare, Dept Cardiol, West Roxbury, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Drenos, Fotios
    UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Tragante, Vinicius
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    Munroe, Patricia B.
    Queen Mary Univ London, William Harvey Res Inst, Natl Inst Hlth Res, Cardiovasc Biomed Res Unit, London, England..
    Malik, Rainer
    Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany..
    Dichgans, Martin
    Univ Munich, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany.;Munich Cluster Syst Neurol SyNergy, Munich, Germany..
    Worrall, Bradford B.
    Univ Virginia, Dept Neurol, Charlottesville, VA USA.;Univ Virginia, Dept Hlth Evaluat Sci, Charlottesville, VA USA..
    Erdmann, Jeanette
    Univ Lubeck, Inst Integrat & Expt Genom, Lubeck, Germany..
    Nelson, Christopher P.
    Univ Leicester, Glenfield Hosp, British Heart Fdn Cardiovasc, Res Ctr,Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, Natl Inst Hlth Res Leicester, Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Samani, Nilesh J.
    Univ Leicester, Glenfield Hosp, British Heart Fdn Cardiovasc, Res Ctr,Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, Natl Inst Hlth Res Leicester, Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Schunkert, Heribert
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;German Ctr Cardiovasc Res, DZHK, Munich Heart Alliance, Partner Site, Munich, Germany..
    Marchini, Jonathan
    Univ Oxford, Dept Stat, Oxford, England..
    Patel, Riyaz S.
    UCL, Inst Cardiovasc Sci, Genet Epidemiol Res Grp, London, England.;Barts Heart Ctr, London, England.;UCL, Farr Inst Hlth Informat, London, England..
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, Genet Epidemiol Res Grp, London, England..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    de Graaf, Jacqueline
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands.;Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, Nijmegen, Netherlands..
    Kiemeney, Lambertus A. L. M.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Nijmegen, Netherlands..
    Baumeister, Sebastian E.
    Univ Med Greifswald, Inst Community Med, Dept SHIP KEF, Greifswald, Germany.;Univ Regensburg, Inst Epidemiol & Prevent Med, Regensburg, Germany..
    Franco, Oscar H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Hofman, Albert
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Uitterlinden, Andre G.
    Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands..
    Koenig, Wolfgang
    German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany..
    Meisinger, Christa
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Peters, Annette
    German Ctr Cardiovasc Res, DZHK, Partner Site, Greifswald, Germany.;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Thorand, Barbara
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol P C5, Leiden, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands..
    Eriksen, Bjorn Odvar
    UiT Arctic Univ Norway, Metab & Renal Res Grp, Tromso, Norway.;Univ Hosp North Norway, Nephrol Sect, Tromso, Norway..
    Toft, Ingrid
    Univ Hosp North Norway, Nephrol Sect, Tromso, Norway..
    Wilsgaard, Tom
    UiT Arctic Univ Norway, Dept Community Med, Tromso, Norway..
    Onland-Moret, N. Charlotte
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    Debette, Stephanie
    Univ Bordeaux, INSERM, U1219, Team Vintage, Bordeaux, France..
    Kumari, Meena
    Univ Essex, Biol & Social Epidemiol, Inst Social & Econ Res, Colchester CO4 3SQ, Essex, England..
    Svensson, Per
    Karolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden.;Karolinska Inst, Dept Med Solna, Stockholm, Sweden..
    van der Harst, Pim
    ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    Kivimaki, Mika
    UCL, Dept Epidemiol & Publ Hlth, London, England..
    Keating, Brendan J.
    Univ Penn, Dept Surg, Div Transplantat, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Sattar, Naveed
    Univ Glasgow, Glasgow, Lanark, Scotland..
    Dehghan, Abbas
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands..
    Reiner, Alex P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    den Ruijter, Hester M.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands..
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.;Univ Med Ctr Utrecht, Ctr Mol Med, Dept Med Genet, Utrecht, Netherlands..
    Pasterkamp, Gerard
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.;Univ Med Ctr Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, Utrecht, Netherlands..
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Holmes, Michael V.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England.;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit CTSU, Richard Doll Bldg,Old Rd Campus,Roosevelt Dr, Oxford OX3 7LF, England..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands.;ICIN Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands.;UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England..
    Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 68, no 9, p. 934-945Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. OBJECTIVES The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. METHODS We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. RESULTS Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 x 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 x 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence fora causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0,994), which was statistically different from the observational estimate (p = 1.6 x 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. CONCLUSIONS Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.

  • 272.
    van Vliet-Ostaptchouk, J. V.
    et al.
    Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Unit Genet Epidemiol & Bioinformat, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, LifeLines Cohort Study, Groningen, Netherlands..
    den Hoed, Marcel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Addenbrookes Hosp, Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England.
    Luan, J.
    Addenbrookes Hosp, Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England..
    Zhao, J. H.
    Addenbrookes Hosp, Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England..
    Ong, K. K.
    Addenbrookes Hosp, Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England..
    van der Most, P. J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Unit Genet Epidemiol & Bioinformat, Groningen, Netherlands..
    Wong, A.
    UCL, Inst Epidemiol & Hlth Care, MRC Unit Lifelong Hlth & Ageing, London, England..
    Hardy, R.
    UCL, Inst Epidemiol & Hlth Care, MRC Unit Lifelong Hlth & Ageing, London, England..
    Kuh, D.
    UCL, Inst Epidemiol & Hlth Care, MRC Unit Lifelong Hlth & Ageing, London, England..
    van der Klauw, M. M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, LifeLines Cohort Study, Groningen, Netherlands..
    Bruinenberg, M.
    Univ Groningen, Univ Med Ctr Groningen, LifeLines Cohort Study, Groningen, Netherlands..
    Khaw, K. T.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Wolffenbuttel, B. H. R.
    Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, LifeLines Cohort Study, Groningen, Netherlands..
    Wareham, N. J.
    Addenbrookes Hosp, Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England..
    Snieder, H.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Unit Genet Epidemiol & Bioinformat, Groningen, Netherlands..
    Loos, R. J. F.
    Addenbrookes Hosp, Inst Metab Sci, Med Res Council Epidemiol Unit, Cambridge, England.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, Charles Bronfman Inst Personalized Med, Mindich Child Hlth & Dev Inst,Dept Prevent Med, New York, NY 10029 USA..
    Pleiotropic effects of obesity-susceptibility loci on metabolic traits: a meta-analysis of up to 37,874 individuals2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, no 10, p. 2134-2146Article in journal (Refereed)
    Abstract [en]

    Genetic pleiotropy may contribute to the clustering of obesity and metabolic conditions. We assessed whether genetic variants that are robustly associated with BMI and waist-to-hip ratio (WHR) also influence metabolic and cardiovascular traits, independently of obesity-related traits, in meta-analyses of up to 37,874 individuals from six European population-based studies. We examined associations of 32 BMI and 14 WHR loci, individually and combined in two genetic predisposition scores (GPSs), with glycaemic traits, blood lipids and BP, with and without adjusting for BMI and/or WHR. We observed significant associations of BMI-increasing alleles at five BMI loci with lower levels of 2 h glucose (RBJ [also known as DNAJC27], QPTCL: effect sizes -0.068 and -0.107 SD, respectively), HDL-cholesterol (SLC39A8: -0.065 SD, MTCH2: -0.039 SD), and diastolic BP (SLC39A8: -0.069 SD), and higher and lower levels of LDL- and total cholesterol (QPTCL: 0.041 and 0.042 SDs, respectively, FLJ35779 [also known as POC5]: -0.042 and -0.041 SDs, respectively) (all p < 2.4 x 10(-4)), independent of BMI. The WHR-increasing alleles at two WHR loci were significantly associated with higher proinsulin (GRB14: 0.069 SD) and lower fasting glucose levels (CPEB4: -0.049 SD), independent of BMI and WHR. A higher GPS-BMI was associated with lower systolic BP (-0.005 SD), diastolic BP (-0.006 SD) and 2 h glucose (-0.013 SD), while a higher GPS-WHR was associated with lower HDL-cholesterol (-0.015 SD) and higher triacylglycerol levels (0.014 SD) (all p < 2.9 x 10(-3)), independent of BMI and/or WHR. These pleiotropic effects of obesity-susceptibility loci provide novel insights into mechanisms that link obesity with metabolic abnormalities.

  • 273. van Vliet-Ostaptchouk, J. V.
    et al.
    den Hoed, Marcel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Luan, J.
    Zhao, J.
    Ong, K.
    Wong, A.
    Hardy, R.
    Kuh, D.
    Van der Klauw, M.
    Bruinenberg, M.
    Khaw, K. -T
    Wolffenbuttel, B.
    Wareham, N.
    Snieder, H.
    Loos, R.
    Pleiotropic effects of obesity-susceptibility loci on metabolic traits: a meta-analysis of up to 37,874 individuals2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, no 1, p. S158-S158Article in journal (Other academic)
  • 274. van Zuydam, N. R.
    et al.
    Voight, B.
    Ladenvall, C.
    Strawbridge, R.
    Willems, S.
    Hartiala, J.
    Vlacholpoulou, E.
    Mihailov, E.
    Kwee, L.
    Qu, L.
    Goel, A.
    Kumar, Jitender
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Kanoni, S.
    Known SNPs in ADAMTS7, the 9p21 region and UBE2E interact with type 2 diabetes status to modify the risk of coronary artery disease in large populations2013In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 56, p. 76-77Article in journal (Other academic)
  • 275.
    Varga, Tibor V.
    et al.
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.
    Kurbasic, Azra
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.
    Aine, Mattias
    Lund Univ, Skåne Univ Hosp, Div Oncol & Pathol.
    Eriksson, Pontus
    Lund Univ, Skåne Univ Hosp, Div Oncol & Pathol.
    Ali, Ashfaq
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.
    Hindy, George
    Skåne Univ Hosp, Diabet & Cardiovasc Dis Genet Epidemiol.
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Luan, Jian'an
    Univ Cambridge, Epidemiol Unit, Med Res Council.
    Shungin, Dmitry
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.;Umeå Univ, Dept Odontol;Umeå Univ, Dept Publ Hlth & Clin Med.
    Chen, Yan
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.
    Schulz, Christina-Alexandra
    Skåne Univ Hosp, Diabet & Cardiovasc Dis Genet Epidemiol.
    Nilsson, Peter M.
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci.
    Hallmans, Göran
    Umeå Univ, Dept Biobank Res.
    Barroso, Ines
    Wellcome Trust Sanger Inst.;Addenbrookes Hosp, Metab Res Labs, Cambridge, Hosp, Metab Res Labs; Addenbrookes Hosp, NIHR Cambridge BiomeEngland.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr.
    Deloukas, Panos
    Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah.
    Langenberg, Claudia
    Univ Cambridge, Epidemiol Unit, Med Res Council.
    Scott, Robert A.
    Univ Cambridge, Epidemiol Unit, Med Res Council.
    Wareham, Nicholas J.
    Univ Cambridge, Epidemiol Unit, Med Res Council.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford.
    Melander, Olle
    Skåne Univ, Dept Clin Sci Hypertens & Cardiovasc Dis.
    Orho-Melander, Marju
    Skåne Univ Hosp, Diabet & Cardiovasc Dis Genet Epidemiol.
    Renström, Frida
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.;Umeå Univ, Dept Biobank Res.
    Franks, Paul W.
    Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.;Umeå Univ, Dept Publ Hlth & Clin Med;Harvard TH Chan Sch Publ Hlth, Dept Nutr.
    Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults2017In: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685, Vol. 46, no 4, p. 1211-1222Article in journal (Refereed)
    Abstract [en]

    Background: Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids.

    Methods: Participants from the GLACIER Study (N-max = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms;replication, fine-mapping regions and wildcard SNPs for lipid traits) were extracted for association tests with 10-year change in total cholesterol (Delta TC) and triglycerides (Delta TG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; N-max = 8263 participants) were used for replication. We conducted an in silico look-up for association with coronary artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAMplusC4D) Consortium (N similar to 190 000) and functional annotation for the top ranking variants.

    Results: In total, 956 variants were associated (P < 0.01) with either Delta TC or Delta TG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with Delta TG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5 x 10(-8)), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 x 10(-6)). The rs7412 variant at APOE was associated with DTC in GLACIER (P < 1.7 x 10(-6)). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with Delta TC and for Delta TG, respectively (P < 10(-3)). Of these, a variant at CAPN3 (P = 1.2 x 10(-4)), multiple variants at HPR (P-min = 1.5 x 10(-6)) and a variant at SIX5 (P = 1.9 x 10(-4)) showed evidence for association with CAD.

    Conclusions: We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk.

  • 276. Vasan, Senthil K.
    et al.
    Karpe, Fredrik
    Gu, Harvest F.
    Brismar, Kerstin
    Fall, Caroline H.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    FTO Genetic Variants and Risk of Obesity and Type 2 Diabetes: A Meta-Analysis of 28,394 Indians2014In: Obesity, ISSN 1930-7381, E-ISSN 1930-739X, Vol. 22, no 3, p. 964-970Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the magnitude of association of FTO variants with obesity, type 2 diabetes (T2DM), and related traits among Asian Indians. Methods: Random-effect meta-analysis was performed on pooled data from eight studies (n=28,394) for obesity and related traits and six studies (n=24,987) for assessment of T2DM risk in Indians where FTO variants were reported. Results: The minor A-allele of the FTO variant rs9939609 was associated with increased risk of obesity (OR 1.15, 95% CI 1.08-1.21, p=2.14 3 10 25), BMI (b=0.30 kg/m 2, 95% CI 0.21-0.38, p=4.78 3 10211) and other regional adiposity measurements [waist (b50.74 cm, 95% CI 0.49-0.99), HC (b=0.52, 95% CI 0.26-0.78), and waist-hip ratio (WHR) (b50.002, 95% CI 0.001-0.004)] in Indians (p = 0.001). An increased risk for T2DM (OR 1.11; 95% CI 1.04-1.19, p=0.002) was observed, which attenuated when adjusted for age, gender, and BMI (OR 1.09; 95% CI 1.02-1.16, p=0.01). Conclusions: Our study provides evidence of association between common FTO variant and obesity risk among Indians with comparable effect sizes as in Caucasians. The attenuation of FTO-T2DM risk on BMI adjustment reinforces that BMI does not fully account for the adiposity effects among Asian Indians who are more centrally obese.

  • 277. Velasquez, Ilais Moreno
    et al.
    Kumar, Jitender
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bjorkbacka, Harry
    Nilsson, Jan
    Silveira, Angela
    Leander, Karin
    Berglund, Anita
    Strawbridge, Rona J.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Melander, Olle
    Almgren, Peter
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hamsten, Anders
    de Faire, Ulf
    Gigante, Bruna
    Duffy antigen receptor genetic variant and the association with Interleukin 8 levels2015In: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 72, no 2, p. 178-184Article in journal (Refereed)
    Abstract [en]

    The aim of this study is to identify loci associated with circulating levels of Interleukin 8 (IL8). We investigated the associations of 121,445 single nucleotide polymorphisms (SNPs) from the Illumina 200K CardioMetabochip with IL8 levels in 1077 controls from the Stockholm Heart Epidemiology Program (SHEEP) study, using linear regression under an additive model of inheritance. Five SNPs (rs12075A/G, rs13179413C/T, rs6907989T/A, rs9352745A/C, rs1779553T/C) reached the predefined threshold of genome-wide significance (p < 1.0 x 10(-5)) and were tested for in silico replication in three independent populations, derived from the PIVUS, MDC-CC and SCARF studies. IL8 was measured in serum (SHEEP, PIVUS) and plasma (MDC-CC, SCARF). The strongest association was found with the SNP rs12075 A/G, Asp42Gly (p = 1.6 x 10(-6)), mapping to the Duffy antigen receptor for chemokines (DARC) gene on chromosome 1. The minor allele G was associated with 15.6% and 10.4% reduction in serum IL8 per copy of the allele in SHEEP and PIVUS studies respectively. No association was observed between rs12075 and plasma IL8. Conclusion: rs12075 was associated with serum levels but not with plasma levels of IL8. It is likely that serum IL8 represents the combination of levels of circulating plasma IL8 and additional chemokine liberated from the erythrocyte DARC reservoir due to clotting. These findings highlight the importance of understanding ILS as a biomarker in cardiometabolic diseases. 

  • 278. Velasquez, Ilais Moreno
    et al.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Leander, Karin
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Gigante, Bruna
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Interleukin-8 is associated with increased total mortality in women but not in men-findings from a community-based cohort of elderly2015In: Annals of Medicine, ISSN 0785-3890, E-ISSN 1365-2060, Vol. 47, no 1, p. 28-33Article in journal (Refereed)
    Abstract [en]

    Objective. To elucidate the association among circulating IL-8 and total mortality in a cohort of elderly, and to explore potential sex differences in the observed association. Methods. The Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) is a cohort of 70-year-old men and women living in Uppsala, Sweden; baseline period: 2001-2004. IL-8 serum measurements were performed in 1003 participants. Results. In total, 61 men and 40 women died during follow-up (median 7.9 years). Baseline IL-8 concentrations were higher in women than in men (P = 0.03). In a multivariable model adjusting for age, established cardiovascular risk factors, and C-reactive protein, log-transformed standard deviation increments in IL-8 levels were weakly associated with an increased risk for total mortality (hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.02 -1.23, P < 0.05) in the whole cohort. Stratified analysis revealed an association in women (HR 1.18, 95% CI 1.06-1.30, P < 0.01) but not in men (HR 0.98, 95% CI 0.76-1.26). Conclusions. A weak association between IL-8 serum levels and an increased risk for mortality was observed. The prospective data support the role of IL-8 as a biomarker of interest; yet, further studies are warranted to elucidate validity of our finding and the possibility of a sex difference.

  • 279. Vimaleswaran, Karani S
    et al.
    Cavadino, Alana
    Berry, Diane J
    Jorde, Rolf
    Dieffenbach, Aida Karina
    Lu, Chen
    Alves, Alexessander Couto
    Heerspink, Hiddo J Lambers
    Tikkanen, Emmi
    Eriksson, Joel
    Wong, Andrew
    Mangino, Massimo
    Jablonski, Kathleen A
    Nolte, Ilja M
    Houston, Denise K
    Ahluwalia, Tarunveer Singh
    van der Most, Peter J
    Pasko, Dorota
    Zgaga, Lina
    Thiering, Elisabeth
    Vitart, Veronique
    Fraser, Ross M
    Huffman, Jennifer E
    de Boer, Rudolf A
    Schöttker, Ben
    Saum, Kai-Uwe
    McCarthy, Mark I
    Dupuis, Josée
    Herzig, Karl-Heinz
    Sebert, Sylvain
    Pouta, Anneli
    Laitinen, Jaana
    Kleber, Marcus E
    Navis, Gerjan
    Lorentzon, Mattias
    Jameson, Karen
    Arden, Nigel
    Cooper, Jackie A
    Acharya, Jayshree
    Hardy, Rebecca
    Raitakari, Olli
    Ripatti, Samuli
    Billings, Liana K
    Lahti, Jari
    Osmond, Clive
    Penninx, Brenda W
    Rejnmark, Lars
    Lohman, Kurt K
    Paternoster, Lavinia
    Stolk, Ronald P
    Hernandez, Dena G
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mellström, Dan
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Tzoulaki, Ioanna
    McLachlan, Stela
    Theodoratou, Evropi
    Tiesler, Carla M T
    Jula, Antti
    Navarro, Pau
    Wright, Alan F
    Polasek, Ozren
    Wilson, James F
    Rudan, Igor
    Salomaa, Veikko
    Heinrich, Joachim
    Campbell, Harry
    Price, Jacqueline F
    Karlsson, Magnus
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Bandinelli, Stefania
    Frayling, Timothy M
    Hartman, Catharina A
    Sørensen, Thorkild I A
    Kritchevsky, Stephen B
    Langdahl, Bente Lomholt
    Eriksson, Johan G
    Florez, Jose C
    Spector, Tim D
    Lehtimäki, Terho
    Kuh, Diana
    Humphries, Steve E
    Cooper, Cyrus
    Ohlsson, Claes
    März, Winfried
    de Borst, Martin H
    Kumari, Meena
    Kivimaki, Mika
    Wang, Thomas J
    Power, Chris
    Brenner, Hermann
    Grimnes, Guri
    van der Harst, Pim
    Snieder, Harold
    Hingorani, Aroon D
    Pilz, Stefan
    Whittaker, John C
    Järvelin, Marjo-Riitta
    Hyppönen, Elina
    Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study2014In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 2, no 9, p. 719-729Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk.

    METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium.

    FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002).

    INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

  • 280.
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    Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
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    Harvard Med Sch, Hebrew SeniorLife, Boston, MA USA.;Framingham Heart Dis Epidemiol Study, Natl Heart Lung & Blood Inst, Framingham, MA USA..
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    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Erzurumluoglu, A. Mesut
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
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    Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England. Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
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    William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, Barts & London Sch Med & Dent, London, England..
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    William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, Barts & London Sch Med & Dent, London, England..
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    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
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    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
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    Vrije Univ, VU Univ Med Ctr, EMGO Inst, Dept Biol Psychol, Amsterdam, Netherlands..
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    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ, Ctr Mol Med, Solna, Sweden..
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    Childrens Hosp, Div Endocrinol, Boston, MA USA.;Broad Inst Harvard & MIT, Cambridge, MA USA..
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    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA USA..
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    Univ Lausanne Hosp, Inst Social & Prevent Med, Lausanne, Switzerland.;Swiss Inst Bioinformat, Lausanne, Switzerland..
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    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
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    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
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    Univ Med Greifswald, Inst Community Med, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
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    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany..
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    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA..
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    Erasmus MC, Genet Epidemiol Unit, Dept Epidemiol, Rotterdam, Netherlands..
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    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
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    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Tampere, Finland..
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    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
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    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge, England..
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    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, Graz, Austria.;Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria..
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    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
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    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
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    Ist Sci San Raffaele, Div Genet & Cell Biol, Milan, Italy..
    Havulinna, Aki S.
    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
    Goel, Anuj
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England..
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    NIA, Neurogenet Lab, Bethesda, MD 20892 USA.;Data Tecn Int, Glen Echo, MD USA..
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    Univ Tartu, Inst Biomed & Translat Med, Tartu, Estonia..
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    IRCCS Burlo Garofolo Children Hosp, Med Genet, Trieste, Italy.;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
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    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge, England..
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    Univ Lubeck, Inst Biomed, Affiliated Inst, Eurac Res, Bolzano, Italy..
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    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY USA.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA..
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    IMIM, Cardiovasc Epidemiol & Genet, Barcelona, Spain.;CIBERCV, Barcelona, Spain..
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    CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy..
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    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Beaumont Hosp, Dept Psychiat, Royal Coll Surg Ireland, Educ & Res Ctr, Dublin, Ireland.;Univ Coll Dublin, UCD Conway Inst, Ctr Proteome Res, Belfield, Ireland.;Univ Coll Dublin, Sch Med, Conway Inst, Belfield, Ireland..
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    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
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    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
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    Univ Michigan, Dept Biostat, Ann Arbor, MI USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI USA..
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    Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
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    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
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    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, Med Genet Sect, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
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    London North West Healthcare NHS Trust, Dept Med Biol, Fac Med, Southall, Middx, England..
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    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA..
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    William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, Barts & London Sch Med & Dent, London, England..
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    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
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    Busselton Populat Med Res Inst, Nedlands, WA, Australia.;PathWest Lab Med Western Australia, Nedlands, WA, Australia.;Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA, Australia..
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    William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, Barts & London Sch Med & Dent, London, England..
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    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
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    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
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    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.;London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England..
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    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
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    NHGRI, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
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    Univ Dundee, Ninewells Hosp & Med Sch, Dundee, Scotland..
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    Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne, Tyne & Wear, England..
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    Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands..
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    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England..
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    Hunter Med Res Inst, New Lambton, NSW, Australia..
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    Busselton Populat Med Res Inst, Nedlands, WA, Australia.;PathWest Lab Med Western Australia, Nedlands, WA, Australia.;Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA, Australia.;Univ Western Australia, Sch Populat & Global Hlth, Nedlands, WA, Australia..
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    Imperial Coll London, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England.;Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland.;Univ Oulu, Bioctr Oulu, Oulu, Finland.;Oulu Univ Hosp, Unit Primary Care, Oulu, Finland..
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    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
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    Framingham Heart Dis Epidemiol Study, Natl Heart Lung & Blood Inst, Framingham, MA USA.;NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Bldg 10, Bethesda, MD 20892 USA..
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    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
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    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
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    Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.;Univ Tampere, Dept Clin Physiol, Fac Med & Life Sci, Tampere, Finland..
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    Univ Cambridge, Dept Publ Hlth & Primary Care, Inst Publ Hlth, Cambridge, England..
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    Univ Split, Dept Publ Hlth, Fac Med, Split, Croatia..
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    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
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    Univ Hosp Geneva, Dept Med Specialties, Cardiol, Geneva, Switzerland..
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    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
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    Univ Hosp Geneva, Dept Med Specialties, Cardiol, Geneva, Switzerland..
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    Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne, Tyne & Wear, England..
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    William Harvey Res Inst, Clin Pharmacol, London, England..
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    Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Dept Psychiat, Amsterdam, Netherlands..
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    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
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    Univ Edinburgh, Sch Mol Genet & Populat Hlth Sci, Sch Med, Teviot Pl, Edinburgh, Midlothian, Scotland..
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    Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol Human Genet & Environm Sci, Sch Publ Hlth, Houston, TX USA..
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    NIH, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA..
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    Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Sch Med, Baltimore, MD USA..
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    CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy..
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    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
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    Erasmus MC, Genet Epidemiol Unit, Dept Epidemiol, Rotterdam, Netherlands..
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    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
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    Univ Edinburgh, Generat Scotland, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.;Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci,Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland.;Univ Glasgow, Inst Cardiovasc & Med Sci, Fac Med, Glasgow, Lanark, Scotland..
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    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
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    McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
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    Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
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    Imperial Coll London, Sch Publ Hlth, London, England..
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    Univ Lubeck, Inst Biomed, Affiliated Inst, Eurac Res, Bolzano, Italy.;Dept Neurol, Gen Cent Hosp, Bolzano, Italy.;Univ Lubeck, Dept Neurol, Lubeck, Germany..
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    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland..
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    William Harvey Res Inst, Clin Pharmacol, London, England.;Fujian Med Univ, Fujian Prov Hosp, Dept Cardiol, Fuzhou, Fujian, Peoples R China..
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    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
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    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
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    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
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    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
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    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, Trieste, Italy..
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    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat & Med, LABioMed, Torrance, CA USA..
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    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
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    Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Graz, Austria..
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    Univ Lubeck, Inst Biomed, Affiliated Inst, Eurac Res, Bolzano, Italy.;INSERM U1078, Etab Francais Sang, Brest, France..
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    Ist Sci San Raffaele, Div Genet & Cell Biol, Milan, Italy..
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    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
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    Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, Graz, Austria..
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    Hunter Med Res Inst, New Lambton, NSW, Australia.;Univ Newcastle, Fac Hlth, Callaghan, NSW, Australia.;John Hunter Hosp, New Lambton, NSW, Australia..
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    Univ Groningen, Univ Med Ctr Groningen, Div Nephrol, Dept Internal Med, Groningen, Netherlands..
    Shields, Denis C.
    Univ Coll Dublin, Sch Med, Conway Inst, Belfield, Ireland..
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    New York Acad Med, New York, NY USA..
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    CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy.;IRCCS Neuromed, Pozzilli, Isernia, Italy..
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    Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin 2, Ireland..
    Stott, David J.
    Univ Glasgow, Inst Cardiovasc & Med Sci, Fac Med, Glasgow, Lanark, Scotland..
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    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Swertz, Morris
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
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    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles BioMed Res Inst, Torrance, CA USA.;Harbor UCLA Med Ctr, Div Genet Outcomes, Dept Pediat, Torrance, CA USA..
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    Imperial Coll London, Int Ctr Circulatory Hlth, London, England..
    Tzoulaki, Ioanna
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Tzourio, Christophe
    Bordeaux Populat Hlth Ctr, INSERM U 1219, Bordeaux, France.;Bordeaux Univ, Bordeaux, France.;Bordeaux Univ Hosp, Dept Publ Hlth, Bordeaux, France.;Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Volker, Uwe
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
    Vollenweider, Peter
    Univ Lausanne Hosp, CHUV, Dept Internal Med, Lausanne, Switzerland..
    Wild, Sarah
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Willemsen, Gonneke
    Vrije Univ, VU Univ Med Ctr, EMGO Inst, Dept Biol Psychol, Amsterdam, Netherlands..
    Wright, Alan F.
    Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Yao, Jie
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, Torrance, CA USA..
    Theriault, Sebastien
    McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
    Conen, David
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Attia, John
    Hunter Med Res Inst, New Lambton, NSW, Australia.;Univ Newcastle, Fac Hlth, Callaghan, NSW, Australia.;John Hunter Hosp, New Lambton, NSW, Australia..
    Sever, Peter
    Imperial Coll London, Natl Heart & Lung Inst, London, England..
    Debette, Stephanie
    Bordeaux Populat Hlth Ctr, INSERM U 1219, Bordeaux, France.;Bordeaux Univ, Bordeaux, France.;Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, London, England..
    Spector, Tim D.
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Palmer, Colin N. A.
    Univ Dundee, Med Res Inst, Ninewells Hosp, Dundee, Scotland.;Univ Dundee, Sch Med, Dundee, Scotland..
    Vergnaud, Anne-Claire
    Imperial Coll London, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Loos, Ruth J. F.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge, England.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth Dev Inst, New York, NY USA..
    Polasek, Ozren
    Univ Split, Dept Publ Hlth, Fac Med, Split, Croatia..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland..
    Girotto, Giorgia
    IRCCS Burlo Garofolo Children Hosp, Med Genet, Trieste, Italy.;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Hayward, Caroline
    Univ Edinburgh, Generat Scotland, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, MRC, Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Kooner, Jaspal S.
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll London, Natl Heart & Lung Inst, Hammersmith Hosp Campus, London, England..
    Lindgren, Cecila M.
    Broad Inst Harvard & MIT, Cambridge, MA USA.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Vitart, Veronique
    Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Univ Leicester, NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England.;Univ Edinburgh, Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Tuomilehto, Jaakko
    Dasman Diabet Inst, Kuwait, Kuwait.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.;Danube Univ Krems, Dept Neurosci & Prevent Med, Krems An Der Donau, Austria. Univ Manchester, Div Cardiovasc Sci, Manchester, Lancs, England..
    Gyllensten, Ulf
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Knekt, Paul
    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Ciullo, Marina
    CNR, Inst Genet & Biophys A Buzzati Traverso, Naples, Italy.;IRCCS Neuromed, Pozzilli, Isernia, Italy..
    Elosua, Roberto
    IMIM, Cardiovasc Epidemiol & Genet, Barcelona, Spain.;CIBERCV, Barcelona, Spain..
    Keavney, Bernard D.
    Cent Manchester Univ Hosp NHS Fdn Trust, Manchester, Lancs, England..
    Hicks, Andrew A.
    Univ Lubeck, Inst Biomed, Affiliated Inst, Eurac Res, Bolzano, Italy..
    Scott, Robert A.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge, England..
    Gasparini, Paolo
    IRCCS Burlo Garofolo Children Hosp, Med Genet, Trieste, Italy.;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Laan, Maris
    Univ Tartu, Inst Biomed & Translat Med, Tartu, Estonia..
    Liu, YongMei
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA..
    Watkins, Hugh
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England..
    Hartman, Catharina A.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Salomaa, Veikko
    Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland..
    Toniolo, Daniela
    Ist Sci San Raffaele, Div Genet & Cell Biol, Milan, Italy..
    Perola, Markus
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Dept Hlth, Helsinki, Finland. Chron Dis Prevent Unit, Helsinki, Finland. Natl Inst Hlth & Welf, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
    Wilson, James F.
    Univ Edinburgh, Ctr Global Hlth Res, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland..
    Schmidt, Helena
    Med Univ Graz, Dept Neurol, Graz, Austria.;Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Graz, Austria..
    Zhao, Jing Hua
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge, England..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Tampere, Finland..
    van Duijn, Cornelia M.
    Erasmus MC, Genet Epidemiol Unit, Dept Epidemiol, Rotterdam, Netherlands..
    Gudnason, Vilmundur
    Icelandic Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.;Kaiser Permanent, Washington Hlth Res Inst, Seattle, WA USA..
    Peters, Annette
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Munich, Germany..
    Rettig, Rainer
    Univ Med Greifswald, Inst Physiol, Karlsburg, Germany..
    James, Alan
    Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA, Australia.;Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep, Nedlands, WA, Australia..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Strachan, David P.
    St Georges Univ London, Populat Hlth Res Inst, London, England..
    Palmas, Walter
    Columbia Univ, Dept Med, Med Ctr, New York, NY USA..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Boomsma, Dorret I.
    Vrije Univ, VU Univ Med Ctr, EMGO Inst, Dept Biol Psychol, Amsterdam, Netherlands..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Bochud, Murielle
    Univ Lausanne Hosp, Inst Social & Prevent Med, Lausanne, Switzerland..
    Newton-Cheh, Christopher
    Broad Inst Harvard & MIT, Cambridge, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Munroe, Patricia B.
    William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, Barts & London Sch Med & Dent, London, England..
    Elliott, Paul
    Imperial Coll London, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, Sch Publ Hlth, London, England..
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Chakravarti, Aravinda
    Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Sch Med, Baltimore, MD USA..
    Knight, Joanne
    Univ Lancaster, Data Sci Inst, Lancaster, England.;Univ Lancaster, Lancaster Med Sch, Lancaster, England..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Levy, Daniel
    NHLBI, Populat Sci Branch, Div Intramural Res, Bldg 10, Bethesda, MD 20892 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Tobin, Martin D.
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Caulfield, Mark J.
    William Harvey Res Inst, Clin Pharmacol, London, England.;Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, Barts & London Sch Med & Dent, London, England..
    Ehret, Georg B.
    Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Sch Med, Baltimore, MD USA.;Univ Hosp Geneva, Dept Med Specialties, Cardiol, Geneva, Switzerland..
    Alistair, T. Y.
    Betholdson, J. -P
    Xiao, Limin
    Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney2017In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 70, no 3, p. E4-e19Article in journal (Refereed)
    Abstract [en]

    Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals. We report 6 new signals of association in or near HSPB7, TNXB, LRP12, LOC283335, SEPT9, and AKT2, and provide new replication evidence for a further 2 signals in EBF2 and NFKBIA. Combining large whole-blood gene expression resources totaling 12 607 individuals, we investigated all novel and previously reported signals and identified 48 genes with evidence for involvement in blood pressure regulation that are significant in multiple resources. Three novel kidney-specific signals were also detected. These robustly implicated genes may provide new leads for therapeutic innovation.

  • 281.
    Walford, Geoffrey A.
    et al.
    Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA 02115 USA..
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Rybin, Denis
    Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA USA..
    Stancakova, Alena
    Univ Eastern Finland, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Chen, Han
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Hong, Jaeyoung
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA..
    Jensen, Richard A.
    Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Med, Seattle, WA USA..
    Rice, Ken
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Toenjes, Anke
    Univ Leipzig, Dept Med, Leipzig, Germany..
    Prokopenko, Inga
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Imperial Coll London, Dept Genom Common Dis, London, England.;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany..
    Delgado, Graciela
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany..
    Silbernagel, Guenther
    Med Univ Graz, Dept Internal Med, Div Angiol, Graz, Austria..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Appel, Emil V.
    Univ Copenhagen, Fac Hlth & Med Sci, Ctr Basic Metab Res, Novo Nordisk Fdn, Copenhagen, Denmark..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Ctr Basic Metab Res, Novo Nordisk Fdn, Copenhagen, Denmark..
    Lewis, Joshua P.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.;Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA..
    Montasser, May E.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.;Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA..
    Ladenvall, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
    Staiger, Harald
    Univ Tubingen Hosp, Div Endocrinol & Diabetol Angiol Nephrol & Clin C, Dept Internal Med, Tubingen, Germany.;German Ctr Diabet Res DZD, Tubingen, Germany.;Univ Tubingen, Helmholtz Ctr Munich, Inst Diabet Res & Metab Dis, Tubingen, Germany..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England..
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Exeter, Devon, England..
    Weedon, Michael N.
    Univ Exeter, Sch Med, Exeter, Devon, England..
    Xie, Weijia
    Univ Exeter, Sch Med, Exeter, Devon, England..
    Morcillo, Sonsoles
    CIBER Pathophysiol Obes & Nutr, Madrid, Spain.;Hosp Reg Univ Malaga, Dept Endocrinol & Nutr, Malaga, Spain..
    Teresa Martinez-Larrad, Maria
    Hosp Clin San Carlos IdISSC, Spanish Biomed Res Ctr Diabet & Associated Metab, Inst Invest Sanitaria, Madrid, Spain..
    Biggs, Mary L.
    Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Chen, Yii-Der Ida
    Harbor UCLA Med Ctr, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Med, LABioMed, Torrance, CA 90509 USA..
    Corbaton-Anchuelo, Arturo
    Hosp Clin San Carlos IdISSC, Spanish Biomed Res Ctr Diabet & Associated Metab, Inst Invest Sanitaria, Madrid, Spain..
    Faerch, Kristine
    Steno Diabet Ctr, Gentofte, Denmark..
    Miguel Gomez-Zumaquero, Juan
    Inst Invest Biomed Malaga IBIMA, Malaga, Spain.;Hosp Carlos Haya Malaga, Sequencing & Genotyping Platform, Malaga, Spain..
    Goodarzi, Mark O.
    Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA..
    Kizer, Jorge R.
    Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.;Montefiore Med Ctr, 111 E 210th St, Bronx, NY 10467 USA.;Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA..
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland.;Minerva Fdn, Inst Med Res, Biomedicum 2U, Helsinki, Finland.;Univ Helsinki, Dept Med, Helsinki, Finland.;Univ Helsinki, Abdominal Ctr Endocrinol, Helsinki, Finland.;Univ Helsinki, Cent Hosp, Helsinki, Finland..
    Leong, Aaron
    Harvard Med Sch, Dept Med, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, Cecilia
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA..
    Machicao, Fausto
    German Ctr Diabet Res DZD, Tubingen, Germany.;Univ Tubingen, Helmholtz Ctr Munich, Inst Diabet Res & Metab Dis, Tubingen, Germany..
    Manning, Alisa K.
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA 02115 USA.;Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA..
    Maria Martin-Nunez, Gracia
    Hosp Reg Univ & Virgen de la Victoria Malaga, Dept Endocrinol & Nutr, Malaga, Spain..
    Rojo-Martinez, Gemma
    Hosp Reg Univ Malaga, Dept Endocrinol & Nutr, Malaga, Spain.;Inst Invest Biomed Malaga IBIMA, Malaga, Spain.;CIBER Diabet & Enfermedades Metab Asociadas CIBER, Madrid, Spain..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Med, LABioMed, Torrance, CA 90509 USA..
    Siscovick, David S.
    Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Med, Seattle, WA USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;New York Acad Med, New York, NY USA..
    Zmuda, Joseph M.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA..
    Zhang, Zhongyang
    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA..
    Serrano-Rios, Manuel
    Hosp Clin San Carlos IdISSC, Spanish Biomed Res Ctr Diabet & Associated Metab, Inst Invest Sanitaria, Madrid, Spain..
    Smith, Ulf
    Univ Gothenburg, Sahlgrenska Acad, Dept Mol & Clin Med, Lundberg Lab Diabet Res, Gothenburg, Sweden..
    Soriguer, Federico
    Hosp Reg Univ Malaga, Dept Endocrinol & Nutr, Malaga, Spain.;Inst Invest Biomed Malaga IBIMA, Malaga, Spain.;CIBER Diabet & Enfermedades Metab Asociadas CIBER, Madrid, Spain..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Ctr Basic Metab Res, Novo Nordisk Fdn, Copenhagen, Denmark..
    Jorgensen, Torben J.
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark.;Aalborg Univ, Fac Med, Aalborg, Denmark.;Res Ctr Prevent & Hlth, Copenhagen, Denmark..
    Linnenberg, Allan
    Res Ctr Prevent & Hlth, Copenhagen, Denmark.;Rigshosp, Dept Clin Expt Res, Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Ctr Basic Metab Res, Novo Nordisk Fdn, Copenhagen, Denmark..
    Walker, Mark
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England..
    Scott, Robert A.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England..
    Fritsche, Andreas
    Univ Tubingen Hosp, Div Endocrinol & Diabetol Angiol Nephrol & Clin C, Dept Internal Med, Tubingen, Germany.;German Ctr Diabet Res DZD, Tubingen, Germany.;Univ Tubingen, Helmholtz Ctr Munich, Inst Diabet Res & Metab Dis, Tubingen, Germany..
    Haering, Hans-Ulrich
    Univ Tubingen Hosp, Div Endocrinol & Diabetol Angiol Nephrol & Clin C, Dept Internal Med, Tubingen, Germany.;German Ctr Diabet Res DZD, Tubingen, Germany.;Univ Tubingen, Helmholtz Ctr Munich, Inst Diabet Res & Metab Dis, Tubingen, Germany..
    Stefan, Norbert
    Univ Tubingen Hosp, Div Endocrinol & Diabetol Angiol Nephrol & Clin C, Dept Internal Med, Tubingen, Germany.;German Ctr Diabet Res DZD, Tubingen, Germany.;Univ Tubingen, Helmholtz Ctr Munich, Inst Diabet Res & Metab Dis, Tubingen, Germany..
    Groop, Leif
    Lund Univ, Ctr Diabet, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    O'Connell, Jeff R.
    Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.;Univ Maryland, Sch Med, Program Personalized & Genom Med, Baltimore, MD 21201 USA..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Bergman, Richard N.
    Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA USA..
    Collins, Francis S.
    NHGRI, Med Genom & Metab Genet Branch, NIH, Bethesda, MD 20892 USA..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Chron Dis Prevent Unit, Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.;Dasman Diabet Inst, Dasman, Kuwait..
    Maerz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Heidelberg, Germany.;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.;Synlab Serv GmbH, Synlab Acad, Mannheim, Germany.;Synlab Serv GmbH, Synlab Acad, Augsburg, Germany..
    Kovacs, Peter
    Univ Leipzig, Integrated Res & Treatment IFB Ctr AdiposityDis, Leipzig, Germany..
    Stumvoll, Michael
    Univ Leipzig, Dept Med, Leipzig, Germany..
    Psaty, Bruce M.
    Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Med, Seattle, WA USA.;Univ Washington, Epidemiol & Hlth Serv, Seattle, WA 98195 USA.;Grp Hlth Res Inst, Seattle, WA USA.;Grp Hlth Cooperat Puget Sound, Seattle, WA USA..
    Kuusisto, Johanna
    Kuopio Univ Hosp, Kuopio, Finland.;Univ Eastern Finland, Dept Med, Kuopio, Finland..
    Laakso, Markku
    Kuopio Univ Hosp, Kuopio, Finland.;Univ Eastern Finland, Dept Med, Kuopio, Finland..
    Meigs, James B.
    Harvard Med Sch, Dept Med, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.;Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA USA..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Florez, Jose C.
    Massachusetts Gen Hosp, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA 02115 USA..
    Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci2016In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 10, p. 3200-3211Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 x 10(-11)), rs12454712 (BCL2; P = 2.7 x 10(-8)), and rs10506418 (FAM19A2; P = 1.9 x 10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.

  • 282. Wandell, Per
    et al.
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sundquist, Jan
    Johansson, Sven-Erik
    Bottai, Matteo
    Sundquist, Kristina
    Effect of cardiovascular drugs on mortality in atrial fibrillation and chronic heart failure2014In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 48, no 5, p. 291-298Article in journal (Refereed)
    Abstract [en]

    Objectives. To study mortality rates among men and women with atrial fibrillation (AF) and concomitant chronic heart failure (CHF) prescribed different classes of cardiovascular drugs in primary health care. Design. A cohort of men (n = 1159) and women (n = 1155) aged 45 years or above and diagnosed with both AF and CHF from patient records from 75 primary care centers in Sweden were included in the study. Regression models with mortality as the outcome were used, with adjustment for a propensity score comprising age, cardiovascular co-morbidities, education, marital status, and pharmacotherapy. We analysed using Cox regression with hazard ratio (HR), and Laplace regression with years until 10% of the patients had died, with 95% confi dence intervals (95% CI). Independent variables were prescribed cardiovascular drugs. Results. Individuals prescribed anticoagulants versus no treatment gained 1.95 years (95% CI 0.47-3.43), anticoagulants versus antiplatelets 1.26 years (95% CI 0.42-2.10), calcium channel blockers 1.17 years (95% CI 0.21-2.14), and statins 1.49 years (95% CI 0.39-2.59). Among patients 80 years or above no significant effect by anticoagulants was seen, HR 0.73 (95% CI 0.43-1.23). Conclusions. Our findings suggest that life may be prolonged in patients with AF and concomitant CHF in primary care prescribed anticoagulants, calcium channel blockers, and statins.

  • 283. Wandell, Per
    et al.
    Ljunggren, Gunnar
    Wahlstrom, Lars
    Carlsson, Axel C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Diabetes and psychiatric illness in the total population of Stockholm2014In: Journal of Psychosomatic Research, ISSN 0022-3999, E-ISSN 1879-1360, Vol. 77, no 3, p. 169-173Article in journal (Refereed)
    Abstract [en]

    Objective: Concomitant psychiatric disorders in people with diabetes affect morbidity and mortality. We aimed to study psychiatric morbidity in people with diabetes and the general population using administrative health care data in Stockholm County. Methods: The study population included all living persons who resided in Stockholm County, Sweden, on January 1, 2011 (N = 2,058,408). Subjects with a diagnosis of diabetes were identified with data from all consultations in primary health care, specialist outpatient care and inpatient care during the time span 2009-2013. As outcome, information was obtained on all consultations due to any psychiatric diagnosis as well as, specifically, schizophrenia, bipolar disorders, depression, and anxiety disorders, in 2011-2013. Analyses were performed by age group and gender. Age-adjusted odds ratios (ORs) with 95% confidence intervals (95% Cl) for women and men with diabetes, using individuals without diabetes as referents, were calculated. Results: Age-adjusted OR for all psychiatric diagnoses among people with diabetes was 1.296 (95% Cl 1.267-1.326) for women and 1.399 (95% Cl 1.368-1.432) for men. The greatest excess risk was found for schizophrenia, with OR 3.439 (95% Cl 3.057-3.868) in women and 2.787 (95% Cl 2.514-3.089) in men, with ORs between 1276 (95% Cl 1227-1327) and 1.714 (95% Cl 1.540-1.905) for the remaining diagnoses. Conclusion: The prevalence of psychiatric disorders is elevated in people with diabetes, which calls for preventive action to be taken to minimize suffering and costs to society.

  • 284.
    Wang, Yunzhang
    et al.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, S-17177 Stockholm, Sweden.
    Karlsson, Robert
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, S-17177 Stockholm, Sweden.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Zhang, Qian
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.
    Hedman, Åsa K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.
    Almgren, Malin
    Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Stockholm, Sweden.
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, S-17177 Stockholm, Sweden;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Stockholm, Sweden.
    McRae, Allan F.
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia.
    Marioni, Riccardo E.
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Dept Psychol, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
    Ingelsson, Erik
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Visscher, Peter M.
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia;Univ Queensland, Queensland Brain Inst, St Lucia, Qld, Australia.
    Deary, Ian J.
    Univ Edinburgh, Dept Psychol, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Morris, Tiffany
    UCL, Canc Inst, London, England.
    Beck, Stephan
    UCL, Canc Inst, London, England.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, S-17177 Stockholm, Sweden.
    Hagg, Sara
    Karolinska Inst, Dept Med Epidemiol & Biostat, Nobels Vag 12A, S-17177 Stockholm, Sweden.
    Epigenetic influences on aging: a longitudinal genome-wide methylation study in old Swedish twins2018In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 13, no 9, p. 975-987Article in journal (Refereed)
    Abstract [en]

    Age-related changes in DNA methylation were observed in cross-sectional studies, but longitudinal evidence is still limited. Here, we aimed to characterize longitudinal age-related methylation patterns using 1011 blood samples collected from 385 Swedish twins (age at entry: mean 69 and standard deviation 9.7, 73 monozygotic and 96 dizygotic pairs) up to five times (mean 2.6) over 20 years (mean 8.7). We identified 1316 age-associated methylation sites (P<1.3x10(-7)) using a longitudinal epigenome-wide association study design. We measured how estimated cellular compositions changed with age and how much they confounded the age effect. We validated the results in two independent longitudinal cohorts, where 118 CpGs were replicated in Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, 390 samples) (P<3.9x10(-5)), 594 in Lothian Birth Cohort (LBC, 3018 samples) (P<5.1x10(-5)) and 63 in both. Functional annotation of age-associated CpGs showed enrichment in CCCTC-binding factor (CTCF) and other transcription factor binding sites. We further investigated genetic influences on methylation and found no interaction between age and genetic effects in the 1316 age-associated CpGs. Moreover, in the same CpGs, methylation differences within twin pairs increased with 6.4% over 10 years, where monozygotic twins had smaller intra-pair differences than dizygotic twins. In conclusion, we show that age-related methylation changes persist in a longitudinal perspective, and are fairly stable across cohorts. The changes are under genetic influence, although this effect is independent of age. Moreover, methylation variability increase over time, especially in age-associated CpGs, indicating the increase of environmental contributions on DNA methylation with age.

  • 285.
    Ward-Caviness, Cavin K.
    et al.
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Xu, Tao
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Aspelund, Thor
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Ctr Publ Hlth, Reykjavik, Iceland..
    Thorand, Barbara
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Montrone, Corinna
    Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, Neuherberg, Germany..
    Meisinger, Christa
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Dunger-Kaltenbach, Irmtraud
    Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, Neuherberg, Germany..
    Zierer, Astrid
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Yu, Zhonghao
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Helgadottir, Inga R.
    Iceland Heart Assoc, Kopavogur, Iceland..
    Harris, Tamara B.
    NIA, Bethesda, MD 20892 USA..
    Launer, Lenore J.
    NIA, Bethesda, MD 20892 USA..
    Ganna, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Eiriksdottir, Gudny
    Iceland Heart Assoc, Kopavogur, Iceland..
    Waldenberger, Melanie
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Prehn, Cornelia
    Helmholtz Zentrum Munchen, Inst Expt Genet, Genome Anal Ctr, Neuherberg, Germany..
    Suhre, Karsten
    Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, Neuherberg, Germany..
    Illig, Thomas
    Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany..
    Adamski, Jerzy
    Helmholtz Zentrum Munchen, Inst Expt Genet, Genome Anal Ctr, Neuherberg, Germany.;Tech Univ Munich, Chair Expt Genet, Munich, Germany..
    Ruepp, Andreas
    Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol, Neuherberg, Germany.;Tech Univ Munich, Chair Expt Genet, Munich, Germany..
    Koenig, Wolfgang
    Univ Ulm, Med Ctr, Dept Internal Med 2, Ulm, Germany.;Tech Univ Munich, Deutsches Herzzentrum, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Emilsson, Valur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Pharmaceut Sci, Reykjavik, Iceland..
    Wang-Sattler, Rui
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany..
    Peters, Annette
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.;Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA..
    Improvement of myocardial infarction risk prediction via inflammation-associated metabolite biomarkers2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 16, p. 1278-1285Article in journal (Refereed)
    Abstract [en]

    Objective The comprehensive assaying of low-molecular-weight compounds, for example, metabolomics, provides a unique tool to uncover novel biomarkers and understand pathways underlying myocardial infarction (MI). We used a targeted metabolomics approach to identify biomarkers for MI and evaluate their involvement in the pathogenesis of MI.

    Methods and results Using three independent, prospective cohorts (KORA S4, KORA S2 and AGES-REFINE), totalling 2257 participants without a history of MI at baseline, we identified metabolites associated with incident MI (266 cases). We also investigated the association between the metabolites and high-sensitivity C reactive protein (hsCRP) to understand the relation between these metabolites and systemic inflammation. Out of 140 metabolites, 16 were nominally associated (p<0.05) with incident MI in KORA S4. Three metabolites, arginine and two lysophosphatidylcholines (LPC 17: 0 and LPC 18:2), were selected as biomarkers via a backward stepwise selection procedure in the KORA S4 and were significant (p<0.0003) in a meta-analysis comprising all three studies including KORA S2 and AGES-REFINE. Furthermore, these three metabolites increased the predictive value of the Framingham risk score, increasing the area under the receiver operating characteristic score in KORA S4 (from 0.70 to 0.78, p=0.001) and AGES-REFINE study (from 0.70 to 0.76, p=0.02), but was not observed in KORA S2. The metabolite biomarkers attenuated the association between hsCRP and MI, indicating a potential link to systemic inflammatory processes.

    Conclusions We identified three metabolite biomarkers, which in combination increase the predictive value of the Framingham risk score. The attenuation of the hsCRP-MI association by these three metabolites indicates a potential link to systemic inflammation.

  • 286.
    Warren, Helen R.
    et al.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England..
    Evangelou, Evangelos
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina, Greece.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina, Greece..
    Cabrera, Claudia P.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England..
    Gao, He
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Ren, Meixia
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England.;Fujian Med Univ, Fujian Prov Hosp, Dept Cardiol, Fuzhou, Peoples R China..
    Mifsud, Borbala
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Ntalla, Ioanna
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Surendran, Praveen
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England..
    Liu, Chunyu
    NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.;Boston Univ, Sch Publ Hlth, Boston, MA USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Kraja, Aldi T.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.;Washington Univ, Sch Med, Ctr Genome Sci & Syst Biol, St Louis, MO 63110 USA..
    Drenos, Fotios
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England.;UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England..
    Loh, Marie
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;ASTAR, Translat Lab Genet Med, Singapore, Singapore..
    Verweij, Niek
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.;Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Marten, Jonathan
    Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Karaman, Ibrahim
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England..
    Lepe, Marcelo P. Segura
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Bayer Pharma, Berlin, Germany..
    O'Reilly, Paul F.
    Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England..
    Knight, Joanne
    Univ Lancaster, Data Sci Inst, Lancaster, England..
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Kato, Norihiro
    Natl Ctr Global Hlth & Med, Res Inst, Dept Gene Diagnost & Therapeut, Tokyo, Japan..
    He, Jiang
    Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA..
    Tai, E. Shyong
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Hlth Syst, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore..
    Said, M. Abdullah
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Porteous, David
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland..
    Alver, Maris
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. Imperial Coll London, Sch Publ Hlth, Imperial Clin Trials Unit, London, England..
    Poulter, Neil
    Farrall, Martin
    Univ Oxford, Radcliffe Dept Med, Wellcome Trust Ctr Human Genet, Div Cardiovasc Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England..
    Gansevoort, Ron T.
    Univ Groningen, Univ Med Ctr Groningen, Dept Nephrol, Groningen, Netherlands..
    Padmanabhan, Sandosh
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.;Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland.;Univ Glasgow, Coll Med Vet & Life Sci, Inst Cardiovasc & Med Sci, British Heart Fdn Glasgow Cardiovasc Res Ctr, Glasgow, Lanark, Scotland..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. Imperial Coll London, Sch Publ Hlth, Imperial Clin Trials Unit, London, England..
    Stanton, Alice
    Royal Coll Surgeons Ireland, Mol & Cellular Therapeut, Dublin, Ireland..
    Connell, John
    Univ Dundee, Ninewells Hosp & Med Sch, Dundee, Scotland..
    Bakker, Stephan J. L.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. Imperial Coll London, Sch Publ Hlth, Imperial Clin Trials Unit, London, England..
    Shields, Denis C.
    Univ Coll Dublin, Conway Inst, Sch Med, Dublin, Ireland..
    Thom, Simon
    Imperial Coll London, Natl Heart & Lung Inst, London, England.;Imperial Coll London, Int Ctr Circulatory Hlth, London, England..
    Brown, Morris
    Sever, Peter
    Imperial Coll London, Natl Heart & Lung Inst, London, England..
    Esko, Tonu
    Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. Imperial Coll London, Sch Publ Hlth, Imperial Clin Trials Unit, London, England.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. Imperial Coll London, Sch Publ Hlth, Imperial Clin Trials Unit, London, England.;Childrens Hosp, Div Endocrinol, 300 Longwood Ave, Boston, MA 02115 USA.;Broad Inst Harvard & MIT, Cambridge, England..
    Hayward, Caroline
    Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland..
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Saleheen, Danish
    Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.;Ctr Noncommun Dis, Karachi, Pakistan.;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Chowdhury, Rajiv
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England..
    Chambers, John C.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Hosp Natl Hlth Serv NHS Trust, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll Healthcare NHS Trust, London, England.;Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Chasman, Daniel I.
    Chakravarti, Aravinda
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA..
    Newton-Cheh, Christopher
    Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.;Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Broad Inst Harvard & MIT, Cambridge, England..
    Lindgren, Cecilia M.
    Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England..
    Levy, Daniel
    NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.;NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.;NHLBI, Framingham Heart Study, Framingham, MA USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Kooner, Jaspal S.
    Imperial Coll London, Natl Heart & Lung Inst, London, England.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll Healthcare NHS Trust, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll London, Cardiovasc Sci, Natl Heart & Lung Inst, Hammersmith Campus, London, England..
    Keavney, Bernard
    Univ Manchester, Fac Biol Med & Hlth, Div Cardiovasc Sci, Manchester, Lancs, England.;Cent Manchester NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Div Med, Manchester, Lancs, England..
    Tomaszewski, Maciej
    Univ Manchester, Fac Biol Med & Hlth, Div Cardiovasc Sci, Manchester, Lancs, England.;Cent Manchester NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Div Med, Manchester, Lancs, England..
    Samani, Nilesh J.
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cardiovasc Epidemiol Unit, Cambridge, England..
    Tobin, Martin D.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Munroe, Patricia B.
    Ehret, Georg B.
    Wain, Louise V.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Barnes, Michael R.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England..
    Tzoulaki, Joanna
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina, Greece.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Caulfield, Mark J.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England.;Queen Mary Univ London, Barts Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England..
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England..
    Vaez, Ahmad
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.;Isfahan Univ Med Sci, Res Inst Primordial Prevent Noncommun Dis, Esfahan, Iran..
    Jansen, Rick
    Vrije Univ Amsterdam, Med Ctr, Dept Psychiat, Neurosci Campus Amsterdam, Amsterdam, Netherlands..
    Joehanes, Roby
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Harvard Med Sch, Hebrew SeniorLife, Boston, MA USA..
    van der Most, Peter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Erzurumluoglu, A. Mesut
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    O'Reilly, Paul
    Kings Coll London, Inst Psychiat Psychol & Neurosci, London, England..
    Rose, Lynda M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Verwoert, Germaine C.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Hottenga, Jouke-Jan
    Vrije Univ, Dept Biol Psychol, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Amsterdam, Netherlands..
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ Sjukhuset, Ctr Mol Med, Solna, Sweden..
    Arking, Dan E.
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA..
    Hwang, Shih-Jen
    NHLBI, Populat Sci Branch, US NIH, Bldg 10, Bethesda, MD 20892 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA USA..
    Guo, Xiuqing
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Kutalik, Zoltan
    Univ Lausanne Hosp, Inst Social & Prevent Med, Lausanne, Switzerland.;Swiss Inst Bioinformat, Lausanne, Switzerland..
    Trompet, Stella
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Shrine, Nick
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
    Ried, Janina S.
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA..
    Smith, Albert V.
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands..
    Nolte, Ilja M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere, Finland..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Wareham, Nicholas J.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Hofer, Edith
    Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria.;Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria..
    Joshi, Peter K.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Kristiansson, Kati
    Natl Inst Hlth & Welf THL, Dept Hlth, Helsinki, Finland..
    Traglia, Michela
    Ist Sci San Raffaele, Div Genet & Cell Biol, Milan, Italy..
    Havulinna, Aki S.
    Natl Inst Hlth & Welf THL, Dept Hlth, Helsinki, Finland..
    Goel, Anuj
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England..
    Nalls, Mike A.
    NIA, Neurogenet Lab, US NIH, Bethesda, MD 20892 USA.;Kelly Serv, Rockville, MD USA..
    Sober, Siim
    Univ Tartu, Inst Mol & Cell Biol, Human Mol Genet Res Grp, Tartu, Estonia..
    Vuckovic, Dragana
    Sidra Med & Res Ctr, Expt Genet Div, Doha, Qatar.;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Luan, Jian'an
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Del Greco M, Fabiola
    European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.;Univ Lubeck, Lubeck, Germany..
    Ayers, Kristin L.
    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Marrugat, Jaume
    IMIM, Cardiovasc Epidemiol & Genet, Barcelona, Spain..
    Ruggiero, Daniela
    CNR, Inst Genet & Biophys Buzzati Traverso, Naples, Italy..
    Lopez, Lorna M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Beaumont Hosp, Educ & Res Ctr, Royal Coll Surg Ireland, Dept Psychiat, Dublin, Ireland.;UCD, Ctr Proteome Res, UCD Conway Inst, Dublin, Ireland..
    Niiranen, Teemu
    Natl Inst Hlth & Welf THL, Dept Hlth, Helsinki, Finland..
    Enroth, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Nelson, Christopher P.
    Univ Leicester, Glenfield Hosp, BHF Cardiovasc Res Ctr, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Huffman, Jennifer E.
    Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Zhang, Weihua
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Gandin, Ilaria
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Harris, Sarah E.
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland..
    Zemonik, Tatijana
    Univ Split, Fac Med, Dept Biol, Split, Croatia..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Shah, Nabi
    Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee, Scotland.;COMSATS Inst Informat Technol, Dept Pharm, Abbottabad, Pakistan..
    de Borst, Martin H.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands..
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.;Natl Inst Hlth Res, Biomed Res Ctr, London, England..
    Prins, Bram P.
    Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England..
    Campbell, Archie
    Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh, Midlothian, Scotland..
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Chauhan, Ganesh
    Bordeaux Populat Hlth Ctr, INSERM, U1219, Bordeaux, France.;Bordeaux Univ, Bordeaux, France..
    Oldmeadow, Christopher
    Hunter Med Res Inst, New Lambton, NSW, Australia..
    Abecasis, Goncalo
    SPH II, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI USA..
    Abedi, Maryam
    Isfahan Univ Med Sci, Dept Genet & Mol Biol, Esfahan, Iran..
    Barbieri, Caterina M.
    Ist Sci San Raffaele, Div Genet & Cell Biol, Milan, Italy..
    Batini, Chiara
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Blake, Tineka
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Braund, Peter S.
    Univ Leicester, Glenfield Hosp, BHF Cardiovasc Res Ctr, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Brumat, Marco
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Cocca, Massimiliano
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Collins, Francis
    NHGRI, Med Genom & Metab Genet Branch, US NIH, Bethesda, MD 20892 USA..
    Cordell, Heather J.
    Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England..
    Damman, Jeffrey J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.;Amsterdam Med Ctr, Dept Pathol, Amsterdam, Netherlands..
    Davies, Gail
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    de Geus, Eco J.
    Vrije Univ, Dept Biol Psychol, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Amsterdam, Netherlands..
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands..
    Deelen, Joris
    Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands..
    Demirkale, Yusuf
    US NIH, Ctr Informat Technol, Bethesda, MD USA..
    Doney, Alex S. F.
    Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee, Scotland..
    Dorr, Marcus
    DZHK German Ctr Cardiovasc Res, Greifswald, Germany.;Univ Med Greifswald, Dept Internal Med B, Greifswald, Germany..
    Ferreira, Teresa
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Franberg, Mattias
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ Sjukhuset, Ctr Mol Med, Solna, Sweden.;Stockholm Univ, Dept Numer Anal & Comp Sci, Stockholm, Sweden..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gieger, Christian
    Helmholtz Zentrum Munchen, Deutsch Forsch Zentrum Gesundheit & Umwelt, Neuherberg, Germany..
    Giulianini, Franco
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA..
    Gow, Alan J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Heriot Watt Univ, Sch Life Sci, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ Sjukhuset, Ctr Mol Med, Solna, Sweden..
    Harris, Tamara B.
    NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA..
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Holliday, Elizabeth G.
    Hunter Med Res Inst, New Lambton, NSW, Australia..
    Jarvelin, Marjo-Riitta
    Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.;Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland.;Univ Oulu, Bioctr Oulu, Oulu, Finland.;Oulu Univ Hosp, Unit Primary Care, Oulu, Finland..
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Johnson, Andrew D.
    NHLBI, Framingham Heart Study, Framingham, MA USA.;NHLBI, Cardiovasc Epidemiol & Human Genom Branch, Bldg 10, Bethesda, MD 20892 USA..
    Jousilahti, Pekka
    Natl Inst Hlth & Welf THL, Dept Hlth, Helsinki, Finland..
    Jula, Antti
    Natl Inst Hlth & Welf THL, Dept Hlth, Helsinki, Finland..
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Physiol, Tampere, Finland..
    Kathiresan, Sekar
    Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England..
    Kolcic, Ivana
    Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia..
    Koskinen, Seppo
    Natl Inst Hlth & Welf THL, Dept Hlth, Helsinki, Finland..
    Langenberg, Claudia
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Larson, Marty
    NHLBI, Framingham Heart Study, Framingham, MA USA..
    Launer, Lenore J.
    NIA, Intramural Res Program, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA..
    Lehne, Benjamin
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England..
    Liewald, David C. M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Lin, Li
    Univ Hosp Geneva, Dept Med, Cardiol, Geneva, Switzerland..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Mach, Francois
    Univ Hosp Geneva, Dept Med, Cardiol, Geneva, Switzerland..
    Mamasoula, Chrysovalanto
    Newcastle Univ, Inst Hlth & Soc, Newcastle Upon Tyne, Tyne & Wear, England..
    Menni, Cristina
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Milaneschi, Yuri
    Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Dept Psychiat, Amsterdam, Netherlands..
    Morgan, Anna
    Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Morris, Andrew D.
    Univ Edinburgh, Sch Med, Sch Mol Genet & Populat Hlth Sci, Edinburgh, Midlothian, Scotland..
    Morrison, Alanna C.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA..
    Munson, Peter J.
    US NIH, Ctr Informat Technol, Bethesda, MD USA..
    Nandakumar, Priyanka
    Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA..
    Nguyen, Quang Tri
    Nutile, Teresa
    CNR, Inst Genet & Biophys Buzzati Traverso, Naples, Italy..
    Oldehinkel, Albertine J.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Oostra, Ben A.
    Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands..
    Org, Elin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia. Imperial Coll London, Sch Publ Hlth, Imperial Clin Trials Unit, London, England..
    Palotie, Aarno
    Univ Helsinki, FIMM, Helsinki, Finland..
    Pare, Guillaume
    McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
    Pattie, Alison
    Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Penninx, Brenda W. J. H.
    Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, Dept Psychiat, Amsterdam, Netherlands..
    Pramstaller, Peter P.
    European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.;Univ Lubeck, Lubeck, Germany.;Gen Cent Hosp, Dept Neurol, Bolzano, Italy.;Univ Lubeck, Dept Neurol, Lubeck, Germany..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland..
    Rice, Kenneth
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Riese, Harriette
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Ripatti, Samuli
    Univ Helsinki, FIMM, Helsinki, Finland..
    Robino, Antonietta
    IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, Italy..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, LABioMed, Dept Med, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Saba, Yasaman
    Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Graz, Austria..
    Saint Pierre, Aude
    European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.;Univ Lubeck, Lubeck, Germany.;Etab Francais Sang, INSERM, U1078, Brest, France..
    Sala, Cinzia F.
    Ist Sci San Raffaele, Div Genet & Cell Biol, Milan, Italy..
    Sarin, Antti-Pekka
    Univ Helsinki, FIMM, Helsinki, Finland..
    Schmidt, Reinhold
    Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria..
    Scott, Rodney
    Hunter Med Res Inst, New Lambton, NSW, Australia.;Univ Newcastle, Fac Hlth, Callaghan, NSW, Australia.;John Hunter Hosp, Sch Biomed Sci & Pharm, New Lambton, NSW, Australia..
    Seelen, Marc A.
    Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, Groningen, Netherlands..
    Siscovick, David
    New York Acad Med, New York, NY USA..
    Sorice, Rossella
    CNR, Inst Genet & Biophys Buzzati Traverso, Naples, Italy.;IRCCS Neuromed, Pozzilli, Italy..
    Stott, David J.
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Swertz, Morris
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    Taylor, Kent D.
    Harbor UCLA Med Ctr, Los Angeles BioMed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.;Harbor UCLA Med Ctr, Dept Pediat, Div Genet Outcomes, Torrance, CA 90509 USA..
    Tzoulaki, Ioanna
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England..
    Tzourio, Christophe
    Bordeaux Populat Hlth Ctr, INSERM, U1219, Bordeaux, France.;Bordeaux Univ, Bordeaux, France.;Bordeaux Univ Hosp, Dept Publ Hlth, Bordeaux, France..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Volker, Uwe
    DZHK German Ctr Cardiovasc Res, Greifswald, Germany.;Univ Med Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany..
    Vollenweider, Peter
    CHU Vaudois, Univ Lausanne Hosp, Dept Internal Med, Lausanne, Switzerland..
    Wild, Sarah
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Willemsen, Gonneke
    Vrije Univ, Dept Biol Psychol, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Amsterdam, Netherlands..
    Wright, Alan F.
    Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Yao, Jie
    Harbor UCLA Med Ctr, LABioMed, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA..
    Theriault, Sebastien
    McMaster Univ, Dept Pathol & Mol Med, Hamilton, ON, Canada..
    Conen, David
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    John, Attia
    Hunter Med Res Inst, New Lambton, NSW, Australia.;Univ Newcastle, Fac Hlth, Callaghan, NSW, Australia.;John Hunter Hosp, Sch Biomed Sci & Pharm, New Lambton, NSW, Australia..
    Debette, Stephanie
    Bordeaux Populat Hlth Ctr, INSERM, U1219, Bordeaux, France.;Bordeaux Univ, Bordeaux, France.;Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge, England..
    Spector, Tim D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee, Scotland..
    Vergnaud, Anne-Claire
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England..
    Loos, Ruth J. F.
    Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth Dev Inst, New York, NY 10029 USA..
    Polasek, Ozren
    Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland..
    Girotto, Giorgia
    Sidra Med & Res Ctr, Expt Genet Div, Doha, Qatar.;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Lindgren, Cecila M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Broad Inst Harvard & MIT, Cambridge, England..
    Vitart, Veronique
    Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.;South Ostrobothnia Cent Hosp, Seinajoki, Finland.;Hosp Univ La Paz, Red RECAVA Grp RD06 0014 0015, Madrid, Spain.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria..
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Knekt, Paul
    Natl Inst Hlth & Welf THL, Dept Hlth, Helsinki, Finland..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland..
    Ciullo, Marina
    CNR, Inst Genet & Biophys Buzzati Traverso, Naples, Italy.;IRCCS Neuromed, Pozzilli, Italy..
    Elosua, Roberto
    IMIM, Cardiovasc Epidemiol & Genet, Barcelona, Spain..
    Keavney, Bernard D.
    Univ Manchester, Fac Biol Med & Hlth, Div Cardiovasc Sci, Manchester, Lancs, England..
    Hicks, Andrew A.
    European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.;Univ Lubeck, Lubeck, Germany..
    Scott, Robert A.
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Gasparini, Paolo
    Sidra Med & Res Ctr, Expt Genet Div, Doha, Qatar.;Univ Trieste, Dept Med Surg & Hlth Sci, Trieste, Italy..
    Laan, Maris
    Univ Tartu, Inst Mol & Cell Biol, Human Mol Genet Res Grp, Tartu, Estonia.;Univ Tartu, Inst Biomed & Translat Med, Tartu, Estonia..
    Liu, YongMei
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA..
    Watkins, Hugh
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England..
    Hartman, Catharina A.
    Univ Groningen, Univ Med Ctr Groningen, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands..
    Salomaa, Veikko
    Natl Inst Hlth & Welf THL, Dept Hlth, Helsinki, Finland..
    Toniolo, Daniela
    Ist Sci San Raffaele, Div Genet & Cell Biol, Milan, Italy..
    Perola, Markus
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland.;Univ Helsinki, FIMM, Helsinki, Finland.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Wilson, James F.
    Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Schmidt, Helena
    Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Graz, Austria.;Med Univ Graz, Dept Neurol, Graz, Austria..
    Zhao, Jing Hua
    Univ Cambridge, MRC Epidemiol Unit, Sch Clin Med, Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere, Finland..
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Psaty, Bruce M.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.;Grp Hlth, Grp Hlth Res Inst, Seattle, WA USA..
    Peters, Annette
    Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany..
    Rettig, Rainer
    Univ Med Greifswald, Inst Physiol, Karlsburg, Germany..
    James, Alan
    Sir Charles Gairdner Hosp, Dept Pulm Physiol & Sleep, Nedlands, WA, Australia.;Univ Western Australia, Sch Med & Pharmacol, Crawley, WA, Australia..
    Jukema, J. Wouter
    Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Strachan, David P.
    St Georges Univ London, Populat Hlth Res Inst, London, England..
    Palmas, Walter
    Columbia Univ, Med Ctr, Dept Med, New York, NY USA..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Boomsma, Dorret I.
    Vrije Univ, Dept Biol Psychol, Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst, Amsterdam, Netherlands..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    Bochud, Murielle
    Univ Lausanne Hosp, Inst Social & Prevent Med, Lausanne, Switzerland..
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk2017In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 49, no 3, p. 403-415Article in journal (Refereed)
    Abstract [en]

    Elevated blood pressure is the leading heritable risk factor for cardiovascular disease worldwide. We report genetic association of blood pressure (systolic, diastolic, pulse pressure) among UK Biobank participants of European ancestry with independent replication in other cohorts, and robust validation of 107 independent loci. We also identify new independent variants at 11 previously reported blood pressure loci. In combination with results from a range of in silico functional analyses and wet bench experiments, our findings highlight new biological pathways for blood pressure regulation enriched for genes expressed in vascular tissues and identify potential therapeutic targets for hypertension. Results from genetic risk score models raise the possibility of a precision medicine approach through early lifestyle intervention to offset the impact of blood pressure-raising genetic variants on future cardiovascular disease risk.

  • 287.
    Wernroth, Mona-Lisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Fall, Katja
    Orebro Univ, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Fang, Fang
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Almqvist, Catarina
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.;Karolinska Univ Hosp, Astrid Lindgren Childrens Hosp, Lung & Allergy Unit, Stockholm, Sweden..
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Dog Exposure During the First Year of Life and Type 1 Diabetes in Childhood2017In: JAMA pediatrics, ISSN 2168-6203, E-ISSN 2168-6211, Vol. 171, no 7, p. 663-669Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The association between early exposure to animals and type 1 diabetes in childhood is not clear. OBJECTIVE To determine whether exposure to dogs during the first year of life is associated with the development of type 1 diabetes in childhood. DESIGN, SETTING, AND PARTICIPANTS A nationwide cohort study utilizing high-quality Swedish national demographic and health registers was conducted. A total of 840 593 children born in Sweden from January 1, 2001, to December 31, 2010, were evaluated. Type 1 diabetes was identified using diagnosis codes from hospitals and dispensed prescriptions of insulin. Cox proportional hazards regression models were used to assess the association between exposure to dogs and risk of type 1 diabetes in childhood. The possible association was further investigated by performing dose-response and breed group-specific analyses. The cohort was followed up until September 30, 2012. Data analysis was conducted from October 15, 2015, to February 8, 2017. EXPOSURES Having a parent who was registered as a dog owner during the child's first year of life. MAIN OUTCOMES AND MEASURES Childhood-onset type 1 diabetes. RESULTS Of the 840 593 children reviewed, 408 272 (48.6%) were girls; mean (SD) age at diagnosis of type 1 diabetes was 5.1 (2.6) years. Dog exposure was identified in 102 035 children (12.1%). Follow-up started at age 1 year, and the children were followed up for as long as 10.7 years (median, 5.5 years). During follow-up, 1999 children developed type 1 diabetes. No association was found between exposure to dogs (adjusted hazard ratio [HR], 1.00; 95% CI, 0.86-1.16) and type 1 diabetes in childhood. The size of the dog (adjusted HR per 10-cm increase in height, 0.96; 95% CI, 0.86-1.06) or number of dogs in the household (1 dog: adjusted HR, 1.07; 95% CI, 0.91-1.26; 2 dogs: 0.79; 95% CI, 0.54-1.15; >= 3 dogs: 0.50; 95% CI, 0.23-1.12; compared with nonexposed children) also was not associated with type 1 diabetes risk. An analysis of children whose parent had type 1 diabetes (210 events) yielded an adjusted HR of 0.71 (95% CI, 0.43-1.17) for dog exposure. CONCLUSIONS AND RELEVANCE In a nationwide study, no evidence supporting an association of register-derived measures of dog exposure with childhood type 1 diabetes was identified.

  • 288. Wessel, Jennifer
    et al.
    Chu, Audrey Y.
    Willems, Sara M.
    Wang, Shuai
    Yaghootkar, Hanieh
    Brody, Jennifer A.
    Dauriz, Marco
    Hivert, Marie-France
    Raghavan, Sridharan
    Lipovich, Leonard
    Hidalgo, Bertha
    Fox, Keolu
    Huffman, Jennifer E.
    An, Ping
    Lu, Yingchang
    Rasmussen-Torvik, Laura J.
    Grarup, Niels
    Ehm, Margaret G.
    Li, Li
    Baldridge, Abigail S.
    Stancakova, Alena
    Abrol, Ravinder
    Besse, Celine
    Boland, Anne
    Bork-Jensen, Jette
    Fornage, Myriam
    Freitag, Daniel F.
    Garcia, Melissa E.
    Guo, Xiuqing
    Hara, Kazuo
    Isaacs, Aaron
    Jakobsdottir, Johanna
    Lange, Leslie A.
    Layton, Jill C.
    Li, Man
    Zhao, Jing Hua
    Meidtner, Karina
    Morrison, Alanna C.
    Nalls, Mike A.
    Peters, Marjolein J.
    Sabater-Lleal, Maria
    Schurmann, Claudia
    Silveira, Angela
    Smith, Albert V.
    Southam, Lorraine
    Stoiber, Marcus H.
    Strawbridge, Rona J.
    Taylor, Kent D.
    Varga, Tibor V.
    Allin, Kristine H.
    Amin, Najaf
    Aponte, Jennifer L.
    Aung, Tin
    Barbieri, Caterina
    Bihlmeyer, Nathan A.
    Boehnke, Michael
    Bombieri, Cristina
    Bowden, Donald W.
    Burns, Sean M.
    Chen, Yuning
    Chen, Yii-Deri
    Cheng, Ching-Yu
    Correa, Adolfo
    Czajkowski, Jacek
    Dehghan, Abbas
    Ehret, Georg B.
    Eiriksdottir, Gudny
    Escher, Stefan A.
    Farmaki, Aliki-Eleni
    Franberg, Mattias
    Gambaro, Giovanni
    Giulianini, Franco
    Goddard, William A., III
    Goel, Anuj
    Gottesman, Omri
    Grove, Megan L.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hai, Yang
    Hallmans, Goeran
    Heo, Jiyoung
    Hoffmann, Per
    Ikram, Mohammad K.
    Jensen, Richard A.
    Jorgensen, Marit E.
    Jorgensen, Torben
    Karaleftheri, Maria
    Khor, Chiea C.
    Kirkpatrick, Andrea
    Kraja, Aldi T.
    Kuusisto, Johanna
    Lange, Ethan M.
    Lee, I. T.
    Lee, Wen-Jane
    Leong, Aaron
    Liao, Jiemin
    Liu, Chunyu
    Liu, Yongmei
    Lindgren, Cecilia M.
    Linneberg, Allan
    Malerba, Giovanni
    Mamakou, Vasiliki
    Marouli, Eirini
    Maruthur, Nisa M.
    Matchan, Angela
    McKean-Cowdin, Roberta
    McLeod, Olga
    Metcalf, Ginger A.
    Mohlke, Karen L.
    Muzny, Donna M.
    Ntalla, Ioanna
    Palmer, Nicholette D.
    Pasko, Dorota
    Peter, Andreas
    Rayner, Nigel W.
    Renstroem, Frida
    Rice, Ken
    Sala, Cinzia F.
    Sennblad, Bengt
    Serafetinidis, Ioannis
    Smith, Jennifer A.
    Soranzo, Nicole
    Speliotes, Elizabeth K.
    Stahl, Eli A.
    Stirrups, Kathleen
    Tentolouris, Nikos
    Thanopoulou, Anastasia
    Torres, Mina
    Traglia, Michela
    Tsafantakis, Emmanouil
    Javad, Sundas
    Yanek, Lisa R.
    Zengini, Eleni
    Becker, Diane M.
    Bis, Joshua C.
    Brown, James B.
    Cupples, L. Adrienne
    Hansen, Torben
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Karter, Andrew J.
    Lorenzo, Carlos
    Mathias, Rasika A.
    Norris, Jill M.
    Peloso, Gina M.
    Sheu, Wayne H. -H.
    Toniolo, Daniela
    Vaidya, Dhananjay
    Varma, Rohit
    Wagenknecht, Lynne E.
    Boeing, Heiner
    Bottinger, Erwin P.
    Dedoussis, George
    Deloukas, Panos
    Ferrannini, Ele
    Franco, Oscar H.
    Franks, Paul W.
    Gibbs, Richard A.
    Gudnason, Vilmundur
    Hamsten, Anders
    Harris, Tamara B.
    Hattersley, Andrew T.
    Hayward, Caroline
    Hofman, Albert
    Jansson, Jan-Hakan
    Langenberg, Claudia
    Launer, Lenore J.
    Levy, Daniel
    Oostra, Ben A.
    O'Donnell, Christopher J.
    O'Rahilly, Stephen
    Padmanabhan, Sandosh
    Pankow, James S.
    Polasek, Ozren
    Province, Michael A.
    Rich, Stephen S.
    Ridker, Paul M.
    Rudan, Igor
    Schulze, Matthias B.
    Smith, Blair H.
    Uitterlinden, Andre G.
    Walker, Mark
    Watkins, Hugh
    Wong, Tien Y.
    Zeggini, Eleftheria
    Laakso, Markku
    Borecki, Ingrid B.
    Chasman, Daniel I.
    Pedersen, Oluf
    Psaty, Bruce M.
    Tai, E. Shyong
    van Duijn, Cornelia M.
    Wareham, Nicholas J.
    Waterworth, Dawn M.
    Boerwinkle, Eric
    Kao, W. H. Linda
    Florez, Jose C.
    Loos, Ruth J. F.
    Wilson, James G.
    Frayling, Timothy M.
    Siscovick, David S.
    Dupuis, Josee
    Rotter, Jerome I.
    Meigs, James B.
    Scott, Robert A.
    Goodarzi, Mark O.
    Sharp, Stephen J.
    Forouhi, Nita G.
    Kerrison, Nicola D.
    Lucarelli, Debora M. E.
    Sims, Matt
    Barroso, Ines
    McCarthy, Mark I.
    Arriola, Larraitz
    Balkau, Beverley
    Barricarte, Aurelio
    Gonzalez, Carlos
    Grioni, Sara
    Kaaks, Rudolf
    Key, Timothy J.
    Navarro, Carmen
    Nilsson, Peter M.
    Overvad, Kim
    Palli, Domenico
    Panico, Salvatore
    Quiros, J. Ramon
    Rolandsson, Olov
    Sacerdote, Carlotta
    Sanchez, Maria-Jose
    Slimani, Nadia
    Tjonneland, Anne
    Tumino, Rosario
    van der A, Daphne L.
    van der Schouw, Yvonne T.
    Riboli, Elio
    Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility2015In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 6, article id 5897Article in journal (Refereed)
    Abstract [en]

    Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.

  • 289.
    Wheeler, Eleanor
    et al.
    Wellcome Trust Sanger Inst, Dept Human Genet, Genome Campus, Cambridge, England..
    Leong, Aaron
    Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA..
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Hivert, Marie-France
    Harvard Pilgrim Hlth Care Inst, Harvard Med Sch, Dept Populat Med, Boston, MA USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ Jukhuset, Ctr Mol Med, Solna, Sweden..
    Podmore, Clara
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.;Lausanne Univ Hosp CHUV, Dept Internal Med, Lausanne, Switzerland..
    Li, Man
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.;Univ Utah, Div Nephrol, Salt Lake City, UT USA.;Univ Utah, Dept Human Genet, Salt Lake City, UT USA..
    Yao, Jie
    LABioMed Harbor UCLA Med Ctr, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Sim, Xueling
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Hong, Jaeyoung
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Chu, Audrey Y.
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Zhang, Weihua
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Wang, Xu
    Natl Univ Singapore, Life Sci Inst, Singapore, Singapore..
    Chen, Peng
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.;Jilin Univ, Minist Educ, Key Lab Pathobiol, Jilin, Jilin, Peoples R China.;Jilin Univ, Coll Basic Med Sci, Changchun, Jilin, Peoples R China..
    Maruthur, Nisa M.
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.;Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA.;Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.;Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore, Singapore..
    Porneala, Bianca C.
    Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA..
    Sharp, Stephen J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Jia, Yucheng
    LABioMed Harbor UCLA Med Ctr, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Kabagambe, Edmond K.
    Vanderbilt Univ, Med Ctr, Dept Med, Div Epidemiol, 221 Kirkland Hall, Nashville, TN 37235 USA..
    Chang, Li-Ching
    Acad Sinica, Inst Biomed Sci, Taipei, Taiwan..
    Chen, Wei-Min
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA..
    Elks, Cathy E.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.;AstraZeneca, Innovat Med & Early Dev Biotech Unit, Personalised Healthcare & Biomarkers, Cambridge, England..
    Evans, Daniel S.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA..
    Fan, Qiao
    Duke NUS Med Sch, Ctr Quantitat Med, Singapore, Singapore..
    Giulianini, Franco
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Go, Min Jin
    Korean Natl Inst Hlth, Ctr Genome Sci, Div Struct & Funct Genom, Osong, Chungchungbuk D, South Korea..
    Hottenga, Jouke-Jan
    Vrije Univ Amsterdam, Biol Psychol, Amsterdam, Netherlands..
    Hu, Yao
    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai, Peoples R China..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Kanoni, Stavroula
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England..
    Kim, Young Jin
    Korean Natl Inst Hlth, Ctr Genome Sci, Div Struct & Funct Genom, Osong, Chungchungbuk D, South Korea..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany..
    Ladenvall, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab. Lund Univ, Lund Univ Diabet Ctr, Lund, Sweden..
    Lecoeur, Cecile
    Univ Lille, CNRS, Inst Pasteur Lille, EGID,UMR 8199, Lille, France..
    Lim, Sing-Hui
    Singapore Eye Res Inst, Acad Level 6, Discovery Tower, Singapore, Singapore..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Marzi, Carola
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Inst Epidemiol 2, Neuherberg, Germany.;German Ctr Diabet Res DZD eV, Partner Munich, Munich, Germany..
    Nalls, Mike A.
    Data Tecn Int, Glen Echo, MD USA.;NIA, Neurogenet Lab, Bethesda, MD 20892 USA..
    Navarro, Pau
    Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Nolte, Ilja M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Rose, Lynda M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Rybin, Denis V.
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.;Boston Univ, Sch Publ Hlth, Data Coordinating Ctr, Boston, MA 02215 USA..
    Sanna, Serena
    CNR, IRGB, Monserrato, Italy..
    Shi, Yuan
    Singapore Eye Res Inst, Acad Level 6, Discovery Tower, Singapore, Singapore..
    Stram, Daniel O.
    Univ Southern Calif, Dept Prevent Med, Los Angeles, CA USA..
    Takeuchi, Fumihiko
    Natl Ctr Global Hlth & Med, Dept Gene Diagnost & Therapeut, Res Inst, Tokyo, Japan..
    Tan, Shu Pei
    Singapore Eye Res Inst, Acad Level 6, Discovery Tower, Singapore, Singapore..
    van der Most, Peter J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Van Vliet-Ostaptchouk, Jana V.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands..
    Wong, Andrew
    MRC Unit Lifelong Hlth & Ageing, London, England..
    Yengo, Loic
    Univ Lille, CNRS, Inst Pasteur Lille, EGID,UMR 8199, Lille, France..
    Zhao, Wanting
    Singapore Eye Res Inst, Acad Level 6, Discovery Tower, Singapore, Singapore..
    Goel, Anuj
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England..
    Martinez Larrad, Maria Teresa
    Spanish Biomed Res Ctr Diabet & Assoc Metab Disor, Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, Madrid, Spain..
    Radke, Doert
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany..
    Salo, Perttu
    Natl Inst Hlth & Welf THL, Helsinki, Finland.;Univ Helsinki, Inst Mol Med, Finland FIMM & Diabet & Obes Res Program, Helsinki, Finland..
    Tanaka, Toshiko
    NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA..
    van Iperen, Erik P. A.
    Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam, Netherlands.;Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, ICIN, Utrecht, Netherlands..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Afaq, Saima
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England..
    Alizadeh, Behrooz Z.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Bertoni, Alain G.
    Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA..
    Bonnefond, Amelia
    Univ Lille, CNRS, Inst Pasteur Lille, EGID,UMR 8199, Lille, France..
    Boettcher, Yvonne
    Univ Leipzig, Integrated Res & Treatment IFB Ctr Adipos Dis, Leipzig, Germany..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Carlson, Olga D.
    NIA, Clin Invest Lab, Baltimore, MD 21224 USA..
    Chen, Chien-Hsiun
    Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.;China Med Univ, Sch Chinese Med, Taichung, Taiwan..
    Cho, Yoon Shin
    Korean Natl Inst Hlth, Ctr Genome Sci, Div Struct & Funct Genom, Osong, Chungchungbuk D, South Korea.;Hallym Univ, Dept Biomed Sci, Chunchon, Gangwon Do, South Korea..
    Garvey, W. Timothy
    Univ Alabama Birmingham, Dept Nutr Sci, Birmingham, AL 35294 USA.;Univ Alabama Birmingham, Birmingham Vet Affairs Med Ctr, Birmingham, AL USA..
    Gieger, Christian
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Inst Epidemiol 2, Neuherberg, Germany..
    Goodarzi, Mark O.
    Cedars Sinai Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA..
    Grallert, Harald
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Inst Epidemiol 2, Neuherberg, Germany.;German Ctr Diabet Res DZD eV, Partner Munich, Munich, Germany..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ Jukhuset, Ctr Mol Med, Solna, Sweden..
    Hartman, Catharina A.
    Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands..
    Herder, Christian
    Univ Dusseldorf, German Diabet Ctr, Leibniz Inst Diabet Res Heinrich Heine, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany..
    Hsiung, Chao Agnes
    Ohio State Univ, Wexner Med Ctr, Dept Internal Med, Div Endocrinol Diabet Metab, Columbus, OH 43210 USA..
    Huang, Jie
    Boston VA Res Inst Inc, Boston, MA USA..
    Igase, Michiya
    Ehime Univ, Grad Sch Med, Dept Geriatr Med, Matsuyama, Ehime, Japan..
    Isono, Masato
    Natl Ctr Global Hlth & Med, Dept Gene Diagnost & Therapeut, Res Inst, Tokyo, Japan..
    Katsuya, Tomohiro
    Osaka Univ, Grad Sch Med, Dept Clin Gene Therapy, Suita, Osaka, Japan.;Osaka Univ, Grad Sch Med, Dept Geriatr Med & Nephrol, Suita, Osaka, Japan..
    Khor, Chiea-Chuen
    Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore..
    Kiess, Wieland
    Univ Leipzig, Univ Hosp Children & Adolescents, Dept Womens & Child Hlth, Ctr Pediat Res, Leipzig, Germany.;Univ Leipzig, LIFE Leipzig Res Ctr Civilizat Dis, LIFE Child, Leipzig, Germany..
    Kohara, Katsuhiko
    Ehime Univ, Fac Collaborat Reg Innovat, Matsuyama, Ehime, Japan..
    Kovacs, Peter
    Univ Leipzig, Integrated Res & Treatment IFB Ctr Adipos Dis, Leipzig, Germany..
    Lee, Juyoung
    Korean Natl Inst Hlth, Ctr Genome Sci, Div Struct & Funct Genom, Osong, Chungchungbuk D, South Korea..
    Lee, Wen-Jane
    Taichung Vet Gen Hosp, Dept Med Res, Taichung, Taiwan..
    Lehne, Benjamin
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England..
    Li, Huaixing
    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai, Peoples R China..
    Liu, Jianjun
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore..
    Lobbens, Stephane
    Univ Lille, CNRS, Inst Pasteur Lille, EGID,UMR 8199, Lille, France..
    Luang, Jian'an
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Lyssenko, Valeriya
    Lund Univ, Lund Univ Diabet Ctr, Lund, Sweden..
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, Munich, Germany.;Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.;Munich Cluster Syst Neurol SyNergy, Munich, Germany.;Singapore Natl Eye Ctr, Singapore, Singapore..
    Miki, Tetsuro
    Ehime Univ, Grad Sch Med, Dept Geriatr Med, Matsuyama, Ehime, Japan..
    Miljkovic, Iva
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA..
    Moon, Sanghoon
    Korean Natl Inst Hlth, Ctr Genome Sci, Div Struct & Funct Genom, Osong, Chungchungbuk D, South Korea..
    Mulas, Antonella
    CNR, IRGB, Monserrato, Italy..
    Mueller, Gabriele
    Univ Hosp & Med Fac Carl Gustav Carus, Ctr Evidence Based Healthcare, Dresden, Germany..
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.;King Abdulaziz Univ, Fand Med Res Ctr, Saudi Diabet Res Grp, Jeddah, Saudi Arabia..
    Nagaraja, Ramaiah
    NIA, Genet Lab, Baltimore, MD 21224 USA..
    Nauck, Matthias
    Univ Med Greifswald, Inst Clin Chem, Greifswald, Germany.;Univ Med Greifswald, Lab Med, Greifswald, Germany..
    Pankow, James S.
    Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Polasek, Ozren
    Univ Split, Split, Croatia.;Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland..
    Prokopenko, Inga
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England..
    Ramos, Paula S.
    Med Univ South Carolina, Dept Med, Charleston, SC USA..
    Rasmussen-Torvik, Laura
    Northwestern Univ Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA..
    Rathmann, Wolfgang
    German Ctr Diabet Res DZD, Neuherberg, Germany..
    Rich, Stephen S.
    Univ Virginia, Sch Med, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA..
    Robertson, Neil R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England..
    Roden, Michael
    Univ Dusseldorf, German Diabet Ctr, Leibniz Inst Diabet Res Heinrich Heine, Inst Clin Diabetol, Dusseldorf, Germany.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Univ Hosp Dusseldorf, Dept Endocrinol & Diabetol, Dusseldorf, Germany..
    Roussel, Ronan
    Ctr Rech Cordelier, INSERM, UMR S 1138, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, UFR Med, Paris, France.;Hop Xavier Bichat, AP HP, DHU FIRE, Dept Diabetol Endocrinol & Nutr, Paris, France..
    Rudan, Igor
    Univ Edinburgh, Edinburgh, Midlothian, Scotland..
    Scott, Robert A.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Scott, William R.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England..
    Sennblad, Bengt
    Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.;Karolinska Univ Jukhuset, Ctr Mol Med, Solna, Sweden.;Karolinska Inst, Sci life Lab, Solna, Sweden..
    Siscovick, David S.
    New York Acad Med, New York, NY USA..
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Munich, Germany..
    Sun, Liang
    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai, Peoples R China..
    Swertz, Morris
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    Tajuddin, Salman M.
    NIA, Hlth Dispar Unit, NIH, Baltimore, MD 21224 USA..
    Taylor, Kent D.
    LABioMed Harbor UCLA Med Ctr, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Teo, Yik-Ying
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Natl Univ Singapore, Life Sci Inst, Singapore, Singapore.;Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore.;Natl Univ Singapore, NUS Grad Sch Integrat Sci & Engn, Singapore, Singapore.;Singapore Natl Eye Ctr, Singapore, Singapore..
    Tham, Yih Chung
    Singapore Eye Res Inst, Acad Level 6, Discovery Tower, Singapore, Singapore..
    Toenjes, Anke
    Univ Leipzig, Dept Med, Leipzig, Germany..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Willemsen, Gonneke
    Vrije Univ Amsterdam, Biol Psychol, Amsterdam, Netherlands..
    Wilsgaard, Tom
    Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway..
    Hingorani, Aroon D.
    UCL, Inst Cardiovasc Sci, London, England..
    Egan, Josephine
    NIA, Clin Invest Lab, Baltimore, MD 21224 USA..
    Ferrucci, Luigi
    NIA, Clin Invest Lab, Baltimore, MD 21224 USA..
    Hovingh, G. Kees
    Acad Med Ctr, Dept Vasc Med, Amsterdam, Netherlands..
    Jula, Antti
    Natl Inst Hlth & Welf THL, Helsinki, Finland..
    Kivimaki, Mika
    UCL, Dept Epidemiol & Publ Hlth, London, England..
    Kumari, Meena
    UCL, Dept Epidemiol & Publ Hlth, London, England.;Univ Essex, Inst Social & Econ Res, Colchester, Essex, England..
    Njolstad, Inger
    Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway..
    Palmer, Colin N. A.
    Med Res Inst, Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogenom, Dundee, Scotland..
    Serrano Rios, Manuel
    Spanish Biomed Res Ctr Diabet & Assoc Metab Disor, Inst Invest Sanitaria Hosp Clin San Carlos IdISSC, Madrid, Spain..
    Stumvoll, Michael
    Univ Leipzig, Dept Med, Leipzig, Germany..
    Watkins, Hugh
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England..
    Aung, Tin
    Singapore Eye Res Inst, Acad Level 6, Discovery Tower, Singapore, Singapore.;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore..
    Blueher, Matthias
    Univ Leipzig, Dept Med, Leipzig, Germany..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Boomsma, Dorret I.
    Vrije Univ Amsterdam, Biol Psychol, Amsterdam, Netherlands..
    Bornstein, Stefan R.
    Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, Dresden, Germany..
    Chambers, John C.
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England..
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Broad Inst MIT & Harvard, Cambridge, MA USA..
    Chen, Yii-Der Ida
    LABioMed Harbor UCLA Med Ctr, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Chen, Yduan-Tsong
    Acad Sinica, Inst Biomed Sci, Taipei, Taiwan..
    Cheng, Ching-Yu
    Singapore Eye Res Inst, Acad Level 6, Discovery Tower, Singapore, Singapore.;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore..
    Cucca, Francesco
    CNR, IRGB, Monserrato, Italy.;Univ Sassari, Dipartimento Sci Biomed, Sassari, Italy..
    de Geus, Eco J. C.
    Vrije Univ Amsterdam, Biol Psychol, Amsterdam, Netherlands..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.;King Abdulaziz Univ, Princess Al Jawhara AI Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Evans, Michele K.
    NIA, Hlth Dispar Unit, NIH, Baltimore, MD 21224 USA..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol, Brown Fdn Inst Mol Med, Houston, TX 77030 USA..
    Friedlander, Yechiel
    Hebrew Univ Jerusalem, Hadassah Med Ctr, Braun Sch Publ Hlth, Jerusalem, Israel..
    Froguel, Philippe
    Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England.;Lille Univ, CNRS 8199, Lille, France..
    Groop, Leif
    Lund Univ, Lund Univ Diabet Ctr, Lund, Sweden.;Finnish Inst Mol Med, Helsinki, Finland..
    Gross, Myron D.
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA..
    Harris, Tamara B.
    NIA, Bethesda, MD 20892 USA..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland..
    Heng, Chew-Kiat
    Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore, Singapore.;Natl Univ Hlth Syst, Khoo Teck Puat Natl Univ Childrens Med Inst, Singapore, Singapore..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Kato, Norihiro
    Natl Ctr Global Hlth & Med, Dept Gene Diagnost & Therapeut, Res Inst, Tokyo, Japan..
    Kim, Bong-Jo
    Korean Natl Inst Hlth, Ctr Genome Sci, Div Struct & Funct Genom, Osong, Chungchungbuk D, South Korea..
    Koh, Woon-Puay
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Duke NUS Med Sch Singapore, Singapore, Singapore..
    Kooner, Jaspal S.
    Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll London, Natl Heart & Lung Inst, Hammersmith Hosp Campus, London, England..
    Koerner, Antje
    Univ Leipzig, Univ Hosp Children & Adolescents, Dept Womens & Child Hlth, Ctr Pediat Res, Leipzig, Germany.;Univ Leipzig, LIFE Leipzig Res Ctr Civilizat Dis, LIFE Child, Leipzig, Germany..
    Kuh, Diana
    MRC Unit Lifelong Hlth & Ageing, London, England..
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med Internal Med, Kuopio, Finland.;Kuopio Univ Hosp, Kuopio, Finland..
    Lin, Xu
    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai, Peoples R China..
    Liu, Yongmei
    Wake Forest Univ, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27109 USA..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth Dev Inst, New York, NY 10029 USA..
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Maerz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany.;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.;Synlab Serv GmbH, Synlab Acad, Mannheim, Germany..
    McCarthy, Mark I.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England..
    Oldehinkel, Albertine J.
    Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands..
    Ong, Ken K.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Pereira, Mark A.
    Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Peters, Annette
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Inst Epidemiol 2, Neuherberg, Germany..
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA.;Harvard Med Sch, Boston, MA USA.;Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA..
    Sabanayagam, Charumathi
    Singapore Eye Res Inst, Acad Level 6, Discovery Tower, Singapore, Singapore.;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore..
    Sale, Michele
    Univ Virginia, Sch Med, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA..
    Saleheen, Danish
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.;Ctr Noncommunicable Dis, Karachi, Pakistan..
    Saltevo, Juha
    Cent Finland, Cent Hosp, Dept Med, Jyvaskyla, Finland..
    Schwarz, Peter E. H.
    Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, Dresden, Germany..
    Sheu, Wayne H. H.
    Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrine & Metab, Taichung, Taiwan.;Natl Yang Ming Univ, Sch Med, Taipei, Taiwan.;Natl Def Med Ctr, Sch Med, Taipei, Taiwan..
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England..
    Tabara, Yasuharu
    Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Chron Dis Prevent Unit, Helsinki, Finland.;Dasman Diabet Inst, Dasman, Kuwait.;Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria..
    van Dam, Rob M.
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Wilson, James F.
    Univ Edinburgh, Western Gen Hosp, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Ctr Global Hlth Res, Edinburgh, Midlothian, Scotland..
    Wolffenbuttel, Bruce H. R.
    Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands..
    Wong, Tien Yin
    Singapore Eye Res Inst, Acad Level 6, Discovery Tower, Singapore, Singapore.;Duke NUS Med Sch, Ophthalmol & Visual Sci Acad Clin Program Eye ACP, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore..
    Wu, Jer-Yuarn
    Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.;China Med Univ, Sch Chinese Med, Taichung, Taiwan..
    Yuan, Jian-Min
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.;Univ Pittsburgh, Inst Canc, Div Canc Control & Populat Sci, Pittsburgh, PA USA..
    Zonderman, Alan B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA..
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Dept Human Genet, Genome Campus, Cambridge, England.;Univ Cambridge, Dept Haematol, Cambridge, England.;Univ Cambridge, Natl Inst Hlth Res Blood & Transplant Unit NIHR B, Cambridge, England..
    Guo, Xiuqing
    LABioMed Harbor UCLA Med Ctr, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Roberts, David J.
    Univ Oxford, Biomed Res Ctr Oxford Haematol Theme, Headley Way, Oxford, England.;Univ Oxford, John Radcliffe Hosp, Radcliffe Dept Med, Headley Way, Oxford, England.;NHS Blood & Transplant, Oxford, England..
    Florez, Jose C.
    Harvard Med Sch, Boston, MA USA.;Massachusetts Gen Hosp, Diabet Unit & Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA..
    Sladek, Robert
    McGill Univ, Dept Med, Montreal, PQ, Canada..
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Morris, Andrew P.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Tai, E-Shyong
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.;Duke NUS Med Sch Singapore, Singapore, Singapore.;Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore, Singapore..
    Selvin, Elizabeth
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.;Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA.;Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.;Singapore Natl Eye Ctr, Singapore, Singapore..
    Rotter, Jerome I.
    LABioMed Harbor UCLA Med Ctr, Dept Pediat, Inst Translat Genom & Populat Sci, Torrance, CA USA..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Dept Human Genet, Genome Campus, Cambridge, England.;Univ Cambridge, Inst Metab Sci, Cambridge, England..
    Meigs, James B.
    Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA.;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA..
    Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis2017In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, no 9, article id e1002383Article in journal (Refereed)
    Abstract [en]

    Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.

    Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.

    Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.

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    Prevent Cardiol & Prevent Med, Dept Med 2, Beijing, Peoples R China.;Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Thrombosis & Hemostasis, Mainz, Germany.;DZHK German Ctr Cardiovasc Res Partner Site Rhine, Mainz, Germany.;Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Cardiol, Langen beckstr 1, D-55131 Mainz, Germany.;Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Thrombosis & Hemostasis, Langen beckstr 1, D-55131 Mainz, Germany..
    Felix, Janine F.
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Room Na 2906,POB 2040, NL-3000 CA Rotterdam, Netherlands..
    Schillert, Arne
    Univ Lubeck, Univ Med Ctr Schleswig Holstein, Inst Med Biometry & Stat, Lubeck, Germany.;DZHK Partner Site Hamburg Kiel Lubeck, Hamburg, Germany..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany.;DZHK Partner Site Greifswald, Greifswald, Germany..
    Chen, Ming-Huei
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA..
    Leening, Maarten J. G.
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Dept Cardiol, Erasmus MC, Rotterdam, Netherlands..
    Voelker, Uwe
    DZHK Partner Site Greifswald, Greifswald, Germany.;Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany..
    Grossmann, Vera
    Johannes Gutenberg Univ Mainz, Univ Med Ctr, Ctr Thrombosis & Hemostasis, Mainz, Germany..
    Brody, Jennifer A.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA..
    Irvin, Marguerite R.
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA..
    Shah, Sanjiv J.
    Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA..
    Pramana, Setia
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Lieb, Wolfgang
    Christian Albrechts Univ Kiel, Inst Epidemiol & Popgen Biobank, Kiel, Germany..
    Schmidt, Reinhold
    Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria..
    Stanton, Alice V.
    Beaumont Hosp, Blood Pressure Unit, Dublin, Ireland.;Royal Coll Surgeons Ireland, Dept Mol & Cellular Therapeut, Dublin, Ireland..
    Malzahn, Doerthe
    Georg August Univ, Univ Med Ctr, Dept Genet Epidemiol, Gottingen, Germany..
    Smith, Albert Vernon
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
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    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Minelli, Cosetta
    Imperial Coll London, Natl Heart & Lung Inst NHLI, Populat Hlth & Occupat Dis, London, England..
    Ruggiero, Daniela
    Inst Genet & Biophys A Buzzati Traverso, CNR, Naples, Italy..
    Lyytikainen, Leo-Pekka
    Dept Clin Chem, Fimlab Labs, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Tampere, Finland..
    Tiller, Daniel
    Martin Luther Univ Halle Wittenberg, Inst Med Epidemiol, Biostat & Informat, Halle, Germany..
    Smith, J. Gustav
    Lund Univ, Dept Cardiol, Lund, Sweden.;Skane Univ Hosp, Lund, Sweden.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Harvard Med Sch, Boston, MA USA..
    Monnereau, Claire
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.;Generat R Study Grp, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Dept Pediat, Erasmus MC, Rotterdam, Netherlands..
    Di Tullio, Marco R.
    Columbia Univ, Med Ctr, Dept Med, New York, NY USA..
    Musani, Solomon K.
    Univ Mississippi, Med Ctr, Jackson Heart Study, Jackson, MS 39216 USA..
    Morrison, Alanna C.
    Univ Texas Hlth Sci Ctr Houston, Dept Epidemiol, Human Genet & Environm Sci, Houston, TX USA..
    Pers, Tune H.
    Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.;Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.;Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark..
    Morley, Michael
    Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany..
    Aragam, Jayashri
    Harvard Med Sch, Boston, MA USA.;Vet Adm Hosp, West Roxbury, Boston, MA USA..
    Benjamin, Emelia J.
    Natl Heart Lung & Blood Inst, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med & Publ Hlth, Sect Cardiol, Prevent Med & Epidemiol, Boston, MA USA..
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA..
    Bisping, Egbert
    Med Univ Graz, Dept Cariol, Graz, Austria..
    Broeckel, Ulrich
    Med Coll Wisconsin, Milwaukee, WI 53226 USA..
    Cheng, Susan
    Natl Heart Lung & Blood Inst, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Harvard Med Sch, Brigham & Womens Hosp, Cardiovasc Div, Boston, MA USA..
    Deckers, Jaap W.
    Univ Med Ctr Rotterdam, Dept Cardiol, Erasmus MC, Rotterdam, Netherlands..
    Del Greco, Fabiola
    Univ Lubeck, European Acad Bolzano Bozen, Ctr Biomed, Lubeck, Germany.;Univ Lubeck, Affiliated Inst, Lubeck, Germany..
    Edelmann, Frank
    Charite Univ Med Berlin, Dept Cardiol, Campus Virchow Klinikum, Berlin, Germany..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr, Houston, TX USA..
    Franke, Lude
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    Friedrich, Nele
    DZHK Partner Site Greifswald, Greifswald, Germany.;Univ Med Greifswald, Inst Clin Chem, Greifswald, Germany.;Univ Med Greifswald, Lab Med, Greifswald, Germany..
    Harris, Tamara B.
    Natl Inst Aging, NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD USA..
    Hofer, Edith
    Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria.;Med Univ Graz, Inst Med Informat, Stat & Documentat, Graz, Austria..
    Hofman, Albert
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands..
    Huang, Jie
    Boston VA Res Inst, Boston, MA USA.;Harvard Med Sch, Brigham & Womens Hosp, Div Aging, Boston, MA USA..
    Hughes, Alun D.
    UCL, Inst Cardiovasc Sci, London, England..
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Physiol, Tampere, Finland..
    Kruppa, Jochen
    Univ Lubeck, Univ Med Ctr Schleswig Holstein, Inst Med Biometry & Stat, Lubeck, Germany.;Univ Vet Med, Fdn Inst Vet Med & Genet, Hannover, Germany..
    Lackner, Karl J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Univ Med Ctr Mainz, Inst Clin Chem & Lab Med, Mainz, Germany.
    Lannfelt, Lars
    Univ Med Ctr Mainz, Dept Med 2, Mainz, Germany..
    Laskowski, Rafael
    Univ Med Ctr Mainz, Dept Med 2, Mainz, Germany..
    Launer, Lenore J.
    Natl Inst Aging, NIH, Neuroepidemiol Sect, Bethesda, MD USA..
    Leosdottir, Margret
    Lund Univ, Dept Cardiol, Lund, Sweden.;Skane Univ Hosp, Malmo, Sweden..
    Lin, Honghuang
    Natl Heart Lung & Blood Inst, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02215 USA..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Univ, Cambridge, MA 02138 USA..
    Loley, Christina
    Univ Lubeck, Univ Med Ctr Schleswig Holstein, Inst Med Biometry & Stat, Lubeck, Germany..
    MacRae, Calum A.
    MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Univ, Cambridge, MA 02138 USA.;Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA..
    Mascalzoni, Deborah
    Univ Lubeck, European Acad Bolzano Bozen, Ctr Biomed, Lubeck, Germany.;Univ Lubeck, Affiliated Inst, Lubeck, Germany..
    Mayet, Jamil
    Hammersmith Hosp, Int Ctr Circulatory Hlth, London, England.;NHLI, Imperial Coll London, London, England..
    Medenwald, Daniel
    Martin Luther Univ Halle Wittenberg, Inst Med Epidemiol, Biostat & Informat, Halle, Germany..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Mueller, Christian
    Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany..
    Mueller-Nurasyid, Martina
    Ludwig Maximilians Univ Munchen, Dept Med 1, Munich, Germany.;DZHK Partner Site Munich Heart Alliance, Munich, Germany.;Inst Genet Epidemiol, Helmholtz Zentrum Munchen German Res Ctr Environm, Neuherberg, Germany..
    Nappo, Stefania
    Inst Genet & Biophys A Buzzati Traverso, CNR, Naples, Italy..
    Nilsson, Peter M.
    Lund Univ, Dept Clin Sci, Malmo, Sweden.;Skane Univ Hosp, Dept Internal Med, Malmo, Sweden..
    Nuding, Sebastian
    Univ Clin Halle Saale, Martin Luther Univ Halle Wittenberg, Dept Med 3, Halle, Germany..
    Nutile, Teresa
    Inst Genet & Biophys A Buzzati Traverso, CNR, Naples, Italy..
    Peters, Annette
    DZHK Partner Site Munich Heart Alliance, Munich, Germany.;Inst Epidemiol II, Helmholtz Zentrum Munchen German Res Ctr Environm, Neuherberg, Germany..
    Pfeufer, Arne
    Inst Human Genet, Helmholtz Zentrum Munchen, Neuherberg, Germany..
    Pietzner, Diana
    Martin Luther Univ Halle Wittenberg, Inst Med Epidemiol, Biostat & Informat, Halle, Germany..
    Pramstaller, Peter P.
    Univ Lubeck, European Acad Bolzano Bozen, Ctr Biomed, Lubeck, Germany.;Univ Lubeck, Affiliated Inst, Lubeck, Germany.;Gen Cent Hosp, Dept Neurol, Bolzano, Italy.;Univ Lubeck, Dept Neurol, Lubeck, Germany..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland..
    Rice, Kenneth M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Rivadeneira, Fernando
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.;Generat R Study Grp, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Dept Internal Med, Erasmus MC, Rotterdam, Netherlands..
    Rotter, Jerome I.
    Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA USA..
    Ruohonen, Saku T.
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland..
    Sacco, Ralph L.
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL USA.;Univ Miami, Miller Sch Med, McKnight Brain Inst Miller, Miami, FL USA.;Univ Miami, Dept Publ Hlth Sci, Miami, FL USA.;Univ Miami, Dept Human Gen, Miami, FL USA..
    Samdarshi, Tandaw E.
    Univ Mississippi, Med Ctr, Div Cardiol, Jackson, MS 39216 USA..
    Schmidt, Helena
    Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria..
    Sharp, Andrew S. P.
    Royal Devon & Exeter Hosp & Univ Exeter, Dept Cardiol, Exeter, Devon, England..
    Shields, Denis C.
    Univ Coll Dublin, UCD Conway Inst Biomol & Biomed Res, Dublin, Ireland.;Univ Coll Dublin, Sch Med & Med Sci, Dublin, Ireland..
    Sorice, Rossella
    Inst Genet & Biophys A Buzzati Traverso, CNR, Naples, Italy.;IRCCS Neuromed, Pozzilli, Isernia, Italy..
    Sotoodehnia, Nona
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Div Cardiol, Seattle, WA 98195 USA..
    Stricker, Bruno H.
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Dept Internal Med, Erasmus MC, Rotterdam, Netherlands.;Inspectorate Hlth Care, Utrecht, Netherlands..
    Surendran, Praveen
    Royal Coll Surgeons Ireland, Dept Mol & Cellular Therapeut, Dublin, Ireland.;Univ Coll Dublin, Sch Med & Med Sci, Dublin, Ireland..
    Thom, Simon
    Hammersmith Hosp, Int Ctr Circulatory Hlth, London, England.;NHLI, Imperial Coll London, London, England..
    Toeglhofer, Anna M.
    Med Univ Graz, Inst Mol Biol & Biochem, Graz, Austria..
    Uitterlinden, Andre G.
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Dept Internal Med, Erasmus MC, Rotterdam, Netherlands..
    Wachter, Rolf
    Georg August Univ, Univ Med Ctr Gottingen, Dept Cardiol & Pneumol, Gottingen, Germany..
    Voelzke, Henry
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany.;DZHK Partner Site Greifswald, Greifswald, Germany..
    Ziegler, Andreas
    Univ Lubeck, Univ Med Ctr Schleswig Holstein, Inst Med Biometry & Stat, Lubeck, Germany.;DZHK Partner Site Hamburg Kiel Lubeck, Hamburg, Germany.;Univ KwaZulu Natal, Sch Math, Stat & Comp Sci, Durban, South Africa.;Univ Lubeck, Zentrum Klin Studien, Lubeck, Germany..
    Muenzel, Thomas
    DZHK German Ctr Cardiovasc Res Partner Site Rhine, Mainz, Germany.;Univ Med Ctr Mainz, Dept Med 2, Mainz, Germany..
    Maerz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany.;Synlab Acad, Synlab Serv GmbH, Mannheim, Germany.;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria..
    Cappola, Thomas P.
    Univ Penn, Perelman Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA.;Univ Penn, Perelman Sch Med, Div Cardiovasc Med, Philadelphia, PA 19104 USA..
    Hirschhorn, Joel N.
    Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.;Harvard Med Sch, Dept Genet, Boston, MA USA..
    Mitchell, Gary F.
    Cardiovasc Engn Inc, Norwood, MA USA..
    Smith, Nicholas L.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA.;Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs Off Res & Dev, Seattle, WA USA..
    Fox, Ervin R.
    Univ Mississippi, Med Ctr, Div Cardiol, Jackson, MS 39216 USA..
    Dueker, Nicole D.
    Univ Miami, Miller Sch Med, John P Hussman Inst Human Gen, Miami, FL USA..
    Jaddoe, Vincent W. V.
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands.;Generat R Study Grp, Rotterdam, Netherlands.;Univ Med Ctr Rotterdam, Dept Pediat, Erasmus MC, Rotterdam, Netherlands..
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden.;Skane Univ Hosp, Dept Internal Med, Malmo, Sweden..
    Russ, Martin
    Univ Clin Halle Saale, Martin Luther Univ Halle Wittenberg, Dept Med 3, Halle, Germany.;Helios Amperklin Dachau, Dachau, Germany..
    Lehtimaki, Terho
    Dept Clin Chem, Fimlab Labs, Tampere, Finland.;Univ Tampere, Fac Med & Life Sci, Dept Clin Chem, Tampere, Finland..
    Ciullo, Marina
    Inst Genet & Biophys A Buzzati Traverso, CNR, Naples, Italy.;IRCCS Neuromed, Pozzilli, Isernia, Italy..
    Hicks, Andrew A.
    Univ Lubeck, European Acad Bolzano Bozen, Ctr Biomed, Lubeck, Germany.;Univ Lubeck, Affiliated Inst, Lubeck, Germany..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Pieske, Burkert
    Med Univ Graz, Dept Cariol, Graz, Austria.;Charite Univ Med Berlin, Dept Cardiol, Campus Virchow Klinikum, Berlin, Germany.;German Heart Inst Berlin DHZB, Dept Internal Med Cardiol, Berlin, Germany..
    Barron, Anthony J.
    Hammersmith Hosp, Int Ctr Circulatory Hlth, London, England.;NHLI, Imperial Coll London, London, England..
    Zweiker, Robert
    Med Univ Graz, Dept Cariol, Graz, Austria..
    Schunkert, Heribert
    DZHK Partner Site Munich Heart Alliance, Munich, Germany.;Tech Univ Munich, Deutsches Herzzentrum, Munich, Germany..
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Liu, Kiang
    Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA..
    Arnett, Donna K.
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA..
    Psaty, Bruce M.
    Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA.;Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Epidemiol & Hlth Serv, Seattle, WA 98195 USA..
    Blankenberg, Stefan
    DZHK Partner Site Hamburg Kiel Lubeck, Hamburg, Germany.;Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany..
    Larson, Martin G.
    Boston Univ, Sch Publ Hlth, Biostat Dept, Boston, MA 02215 USA.;Boston Univ, Dept Math & Stat, Boston, MA USA..
    Felix, Stephan B.
    DZHK Partner Site Greifswald, Greifswald, Germany.;Univ Med Greifswald, Dept Internal Med B, Ferdinand Sauerbruch Str, D-17475 Greifswald, Germany..
    Franco, Oscar H.
    Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, Rotterdam, Netherlands..
    Zeller, Tanja
    DZHK Partner Site Hamburg Kiel Lubeck, Hamburg, Germany.;Univ Heart Ctr Hamburg, Dept Gen & Intervent Cardiol, Hamburg, Germany..
    Vasan, Ramachandran S.
    Natl Heart Lung & Blood Inst, Framingham, MA USA.;Boston Univ Framingham Heart Study, Framingham, MA USA.;Boston Univ, Sch Med & Publ Hlth, Sect Cardiol, Prevent Med & Epidemiol, Boston, MA USA.;Boston Univ, Sch Med & Framingham Heart Study, Dept Med, Sect Prevent Med & Epidemiol & Cardiol, 801 Massachusetts Ave,Suite 470, Boston, MA 02118 USA..
    Doerr, Marcus
    DZHK Partner Site Greifswald, Greifswald, Germany.;Univ Med Greifswald, Dept Internal Med B, Ferdinand Sauerbruch Str, D-17475 Greifswald, Germany..
    Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function2017In: Journal of Clinical Investigation, ISSN 0021-9738, E-ISSN 1558-8238, Vol. 127, no 5, p. 1798-1812Article in journal (Refereed)
    Abstract [en]

    BACKGROUND. Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS. A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS. The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication was performed in 5 cohorts (n = 14,321) and 6 cohorts (n = 16,308), respectively. Besides 5 previously reported loci, the combined meta-analysis identified 10 additional genome-wide significant SNPs: rs12541595 near MTSS1 and rs10774625 in ATXN2 for LV end-diastolic internal dimension; rs806322 near KCNRG, rs4765663 in CACNA1C, rs6702619 near PALMD, rs7127129 in TMEM16A, rs11207426 near FGGY, rs17608766 in GOSR2, and rs17696696 in CFDP1 for aortic root diameter; and rs12440869 in IQCH for Doppler transmitral A-wave peak velocity. Findings were in part validated in other cohorts and in GWAS of related disease traits. The genetic loci showed associations with putative signaling pathways, and with gene expression in whole blood, monocytes, and myocardial tissue. CONCLUSION. The additional genetic loci identified in this large meta-analysis of cardiac structure and function provide insights into the underlying genetic architecture of cardiac structure and warrant follow-up in future functional studies.

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    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
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    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
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    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Spector, Tim D.
    Stefansson, Kari
    Strachan, David P.
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    Tremoli, Elena
    Tuomilehto, Jaakko
    Uusitupa, Matti
    van Duijn, Cornelia M.
    Vollenweider, Peter
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
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    Rich, Stephen S.
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    Kathiresan, Sekar
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    Discovery and refinement of loci associated with lipid levels2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 11, p. 1274-1283Article in journal (Refereed)
    Abstract [en]

    Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.

  • 292. Winkler, Thomas W.
    et al.
    Day, Felix R.
    Croteau-Chonka, Damien C.
    Wood, Andrew R.
    Locke, Adam E.
    Maegi, Reedik
    Ferreira, Teresa
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Graff, Mariaelisa
    Justice, Anne E.
    Luan, Jian'an
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Randall, Joshua C.
    Vedantam, Sailaja
    Workalemahu, Tsegaselassie
    Kilpelainen, Tuomas O.
    Scherag, Andre
    Esko, Tonu
    Kutalik, Zoltan
    Heid, Iris M.
    Loos, Ruth J. F.
    Quality control and conduct of genome-wide association meta-analyses2014In: Nature Protocols, ISSN 1754-2189, E-ISSN 1750-2799, Vol. 9, no 5, p. 1192-1212Article in journal (Refereed)
    Abstract [en]

    Rigorous organization and quality control (QC) are necessary to facilitate successful genome-wide association meta-analyses (GWAMAs) of statistics aggregated across multiple genome-wide association studies. This protocol provides guidelines for (i) organizational aspects of GWAMAs, and for (ii) QC at the study file level, the meta- level across studies and the meta-analysis output level. Real-world examples highlight issues experienced and solutions developed by the GIANT Consortium that has conducted meta-analyses including data from 125 studies comprising more than 330,000 individuals. We provide a general protocol for conducting GWAMAs and carrying out QC to minimize errors and to guarantee maximum use of the data. We also include details for the use of a powerful and flexible software package called EasyQC. Precise timings will be greatly influenced by consortium size. For consortia of comparable size to the GIANT Consortium, this protocol takes a minimum of about 10 months to complete.

  • 293.
    Winkler, Thomas W.
    et al.
    Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany..
    Justice, Anne E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Graff, Mariaelisa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA..
    Barata, Llilda
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA..
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA..
    Chu, Su
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Czajkowski, Jacek
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA..
    Esko, Tonu
    MIT, Broad Inst, Cambridge, MA 02139 USA.;Harvard Univ, Cambridge, MA 02138 USA.;Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Boston Childrens Hosp, Div Genet, Boston, MA USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.;Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA..
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Kilpelainen, Tuomas O.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, Copenhagen, Denmark.;Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    Pers, Tune H.
    Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.;Boston Childrens Hosp, Div Genet, Boston, MA USA.;Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.;Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Med & Populat Genet Program, Cambridge, MA USA..
    Rueeger, Sina
    Swiss Inst Bioinformat, Lausanne, Switzerland.;Univ Hosp Lausanne CHUV, Inst Social & Prevent Med, Lausanne, Switzerland..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, Greifswald, Germany.;Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany..
    Ehret, Georg B.
    Univ Hosp Geneva, Dept Specialties Internal Med, Geneva, Switzerland.;Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA..
    Ferreira, Teresa
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Heard-Costa, Nancy L.
    Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA.;NHLBI, Framingham Heart Study, Framingham, MA USA..
    Karjalainen, Juha
    Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands..
    Lagou, Vasiliki
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Neinast, Michael D.
    Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA..
    Prokopenko, Inga
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Hammersmith Hosp, London, England.;Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England..
    Simino, Jeannette
    Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA..
    Teslovich, Tanya M.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Jansen, Rick
    Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands..
    Westra, Harm-Jan
    Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.;Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Med, Div Rheumatol, Boston, MA 02115 USA.;Harvard Univ, Sch Med, Boston, MA 02115 USA.;Partners Ctr Personalized Genet Med, Boston, MA USA..
    White, Charles C.
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA..
    Absher, Devin
    HudsonAlpha Inst Biotechnol, Huntsville, AL USA..
    Ahluwalia, Tarunveer S.
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, Copenhagen, Denmark.;Steno Diabet Ctr A S, Gentofte, Denmark.;Univ Copenhagen, Herlev & Gentofte Hosp, COPSAC, Copenhagen, Denmark..
    Ahmad, Shafqat
    Skane Univ Hosp Malmo, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden..
    Albrecht, Eva
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany..
    Alves, Alexessander Couto
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC Hlth Protect Agcy HPA Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England..
    Bragg-Gresham, Jennifer L.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    de Craen, Anton J. M.
    Leiden Univ Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands..
    Bis, Joshua C.
    Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Univ Washington, Dept Med, Seattle, WA 98195 USA..
    Bonnefond, Amelie
    CNRS, UMR 8199, Lille, France.;European Genom Inst Diabet, Lille, France.;Univ Lille 2, Lille, France..
    Boucher, Gabrielle
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Cadby, Gemma
    Univ Western Australia, Ctr Genet Origins Hlth & Dis, Crawley, WA, Australia..
    Cheng, Yu-Ching
    VA Maryland Hlth Care Syst, Baltimore, MD USA.;Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA..
    Chiang, Charleston W. K.
    Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA..
    Delgado, Graciela
    Heidelberg Univ, Mannheim Med Fac, Dept Med 5, Mannheim, Germany..
    Demirkan, Ayse
    Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands..
    Dueker, Nicole
    Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA..
    Eklund, Niina
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.;Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland..
    Eiriksdottir, Gudny
    Iceland Heart Assoc, Kopavogur, Iceland..
    Eriksson, Joel
    Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Inst Med,Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Feenstra, Bjarke
    Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark..
    Fischer, Krista
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    Frau, Francesca
    Univ Milan, Dept Hlth Sci, Milan, Italy.;Filarete Fdn, Genom & Bioinformat Unit, Milan, Italy..
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands..
    Geller, Frank
    Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark..
    Goel, Anuj
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovac Med, Oxford, England..
    Gorski, Mathias
    Univ Regensburg, Inst Epidemiol & Prevent Med, Dept Genet Epidemiol, D-93053 Regensburg, Germany.;Univ Hosp Regensburg, Dept Nephrol, Regensburg, Germany..
    Grammer, Tanja B.
    Heidelberg Univ, Mannheim Med Fac, Dept Med 5, Mannheim, Germany..
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Haitjema, Saskia
    UMCU, Expt Cardiol & Lab Clin Chem, Utrecht, Netherlands..
    Hottenga, Jouke-Jan
    Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands..
    Huffman, Jennifer E.
    NHLBI, Framingham Heart Study, Framingham, MA USA.;Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland..
    Jackson, Anne U.
    Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Jacobs, Kevin B.
    NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.;NCI, Core Genotyping Facil, SAIC Frederick Inc, Frederick, MD 21701 USA..
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Kaakinen, Marika
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC Hlth Protect Agcy HPA Ctr Environm & Hlth, Dept Epidemiol & Biostat, London, England.;Univ Oulu, Inst Hlth Sci, Oulu, Finland..
    Kleber, Marcus E.
    Heidelberg Univ, Mannheim Med Fac, Dept Med 5, Mannheim, Germany..
    Lahti, Jari
    Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Inst Behav Sci, Helsinki, Finland..
    Leach, Irene Mateo
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Lehne, Benjamin
    Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England..
    Liu, Youfang
    Univ N Carolina Chapel Hill, Thurston Arthrit Res Ctr, Chaper Hill, NC USA..
    Lo, Ken Sin
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Inst Med,Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    Luan, Jian'an
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England..
    Madden, Pamela A. F.
    Washington Univ, Sch Med, St Louis, MO USA..
    Mangino, Massimo
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England..
    McKnight, Barbara
    Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Biostat & Biomath, Seattle, WA 98104 USA.;Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Medina-Gomez, Carolina
    NCHA, NGI, Leiden, Netherlands.;Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands..
    Monda, Keri L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.;Amgen Inc, Ctr Observat Res, Thousand Oaks, CA 91320 USA..
    Montasser, May E.
    Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr,Program Personalized, Baltimore, MD 21201 USA..
    Mueller, Gabriele
    Univ Dresden, Med Fac Carl Gustav Carus, Ctr Evidence Based Healthcare, Dresden, Germany..
    Mueller-Nurasyid, Martina
    German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.;Univ Munich, Univ Hosp Grosshadern, Dept Med 1, D-81377 Munich, Germany.;Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, D-81377 Munich, Germany.;Munich Heart Alliance, DZHK German Ctr Cardiovasc Res, Munich, Germany..
    Nolte, Ilja M.
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Panoutsopoulou, Kalliope
    Wellcome Trust Sanger Inst, Human Genet, Cambridge, England..
    Pascoe, Laura
    Newcastle Univ, Inst Cell & Mol Biosci, Newcastle, NSW, Australia..
    Paternoster, Lavinia
    Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol, Avon, England..
    Rayner, Nigel W.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.;Wellcome Trust Sanger Inst, Human Genet, Cambridge, England..
    Renstrom, Frida
    Skane Univ Hosp Malmo, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden..
    Rizzi, Federica
    Univ Milan, Dept Hlth Sci, Milan, Italy.;Filarete Fdn, Genom & Bioinformat Unit, Milan, Italy..
    Rose, Lynda M.
    Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA..
    Ryan, Kathy A.
    Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr,Program Personalized, Baltimore, MD 21201 USA..
    Salo, Perttu
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.;Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland..
    Sanna, Serena
    CNR, Ist Ric Genet & Biomed, Monserrato, Italy..
    Scharnagl, Hubert
    Med Univ Graz, Inst Clin Med, Graz, Austria.;Med Univ Graz, Chem Lab Diagnost, Graz, Austria..
    Shi, Jianxin
    NCI, Bethesda, MD 20892 USA..
    Smith, Albert Vernon
    Iceland Heart Assoc, Kopavogur, Iceland.;Univ Iceland, Fac Med, Reykjavik, Iceland..
    Southam, Lorraine
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Wellcome Trust Sanger Inst, Human Genet, Cambridge, England..
    Stancakova, Alena
    Univ Eastern Finland, Dept Med, Kuopio, Finland.;Kuopio Univ Hosp, SF-70210 Kuopio, Finland..
    Steinthorsdottir, Valgerdur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland..
    Strawbridge, Rona J.
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden..
    Sung, Yun Ju
    Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA..
    Tachmazidou, Ioanna
    Wellcome Trust Sanger Inst, Human Genet, Cambridge, England..
    Tanaka, Toshiko
    NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA..
    Thorleifsson, Gudmar
    Amgen Inc, deCODE Genet, Reykjavik, Iceland..
    Trompet, Stella
    Leiden Univ Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands.;Leiden Univ Med Ctr, Dept Cardiol, Leiden, Netherlands..
    Pervjakova, Natalia
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland.;Univ Tartu, Inst Cell & Mol Biol, Dept Biotechnol, EE-50090 Tartu, Estonia.;Univ Helsinki, Helsinki, Finland..
    Tyrer, Jonathan P.
    Univ Cambridge, Dept Oncol, Cambridge, England..
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Ctr Bone & Arthrit Res, Inst Med,Dept Internal Med & Clin Nutr, Gothenburg, Sweden..
    van der Laan, Sander W.
    UMCU, Expt Cardiol & Lab Clin Chem, Utrecht, Netherlands..
    van der Velde, Nathalie
    Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, Dept Internal Med, Geriatr Med Sect, NL-1105 AZ Amsterdam, Netherlands..
    van Setten, Jessica
    Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Neth