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  • 301. Xu, Hong
    et al.
    Huang, Xiaoyan
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Carrero, Juan Jesus
    Fiber Intake, Kidney Function, Inflammation, and Mortality in a Community-Based Cohort2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, p. 49-49Article in journal (Other academic)
  • 302. Xu, Hong
    et al.
    Huang, Xiaoyan
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Carrero, Juan Jesus
    Urinary albumin excretion, blood pressure changes and hypertension incidence in the community: effect modification by kidney function2014In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 29, no 8, p. 1538-1545Article in journal (Refereed)
    Abstract [en]

    Both increased albuminuria and reduced kidney function may predict blood pressure (BP) progression in the community, while they exacerbate each other's effects. We investigated associations and interactions between these two risk factors, BP changes and hypertension incidence in community-dwelling elderly men. Observational study from the Uppsala Longitudinal Study of Adult Men, which included 1051 men (all aged 71 years) with assessments on urinary albumin excretion rate (UAER), 24-hour ambulatory BP monitoring (ABPM) and cystatin-C estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years, and ABPM measurements were again recorded to assess blood pressure changes and hypertension incidence. UAER was found to be associated with ABPM measurements both at baseline and longitudinally. In longitudinal analysis, there were significant interactions between UAER and kidney function in its association with the changes of systolic BP, mean arterial pressure and pulse pressure. After stratification for renal function state, UAER independently predicted BP changes only in those who had eGFR < 60 mL/min/1.73 m(2). At re-examination, 71 new cases of hypertension were recorded. In multivariable logistic models, similar interactions were observed on hypertension incidence: UAER was an independent predictor of incident hypertension only in those with reduced renal function. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER (< 20 A mu g/min). In community-dwelling elderly men, UAER associates with BP progression and hypertension incidence, even within the normal range. Concurrent reduction of renal function modifies and exacerbates these associations.

  • 303. Xu, Hong
    et al.
    Huang, Xiaoyan
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Carrero, Juan Jesús
    Albuminuria, renal dysfunction and circadian blood pressure rhythm in older men: a population-based longitudinal cohort study2015In: Clinical Kidney Journal, ISSN 2048-8505, E-ISSN 2048-8513, Vol. 8, no 5, p. 560-566Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Both albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while exacerbating each other's effects. We investigated associations and interactions of these two risk factors with circadian BP rhythm variation and non-dipper pattern progression in community-dwelling older men.

    METHODS: This was a cross-sectional and longitudinal analyses in the third and fourth cycles of the Uppsala Longitudinal Study of Adult Men, including 1051 men (age 71 years) with assessments on urinary albumin excretion rate (UAER), 24-h ambulatory BP monitoring (ABPM) and cystatin-C-estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years. Study outcomes were ABMP changes and non-dipping BP pattern (prevalence and progression).

    RESULTS: UAER associated with circadian BP rhythm both cross-sectionally and longitudinally. Longitudinally, significant interactions were observed between UAER and kidney dysfunction (eGFR < 60 mL/min/1.73 m(2)) in its association with the changes of both night-time systolic BP (SBP) and night-day SBP ratio. After stratification, UAER strongly predicted night-day SBP ratio change only in those with concurrent kidney dysfunction. At re-examination, 221 new cases of non-dipper were identified. In multivariable logistic models, high UAER associated with increased likelihood of non-dipper progression, but more strongly so among individuals with concurrent kidney dysfunction. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER.

    CONCLUSIONS: UAER associates with circadian BP rhythm variation and non-dipper progression in elderly men. Concurrent renal dysfunction modifies and exacerbates these associations.

  • 304. Xu, Hong
    et al.
    Jia, Ting
    Huang, Xiaoyan
    Riserus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lindholm, Bengt
    Carrero, Juan-Jesus
    Dietary acid load, insulin sensitivity and risk of type 2 diabetes in community-dwelling older men2014In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 57, no 8, p. 1561-1568Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis We tested the hypothesis that dietary acid load may increase the risk of type 2 diabetes, and studied the association between acid load and insulin sensitivity as a possible mechanism involved. Methods An observational survey with prospective follow-up including 911 non-diabetic Swedish men aged 70-71 years was carried out. The gold standard euglycaemic-hyperinsulinaemic clamp technique and the OGTT were used to determine insulin sensitivity and beta cell function, respectively. Diabetes incidence was assessed during 18 years of follow-up. Renal function was estimated from serum cystatin C concentrations. Dietary acid load was calculated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) algorithms from 7 day food records. Adequate dietary reporters were identified by Goldberg cut-offs. Results PRAL and NEAP were not associated with insulin sensitivity or beta cell function. Underlying kidney function or consideration of dietary adequate reporters did not modify these null findings. During follow-up, 115 new cases of diabetes were validated. Neither PRAL nor NEAP was associated with diabetes incidence. Conclusios/interpretation Our results do not support the hypothesis that dietary acid load influences insulin sensitivity, beta cell function or diabetes risk. Interventional studies modifying acid-base dietary intake are needed to further elucidate a possible role of acid load in the development of type 2 diabetes.

  • 305. Yaghootkar, Hanieh
    et al.
    Lamina, Claudia
    Scott, Robert A.
    Dastani, Zari
    Hivert, Marie-France
    Warren, Liling L.
    Stancakova, Alena
    Buxbaum, Sarah G.
    Lyytikaeinen, Leo-Pekka
    Henneman, Peter
    Wu, Ying
    Cheung, Chloe Y. Y.
    Pankow, James S.
    Jackson, Anne U.
    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.
    Zhao, Jing Hua
    Ballantyne, Christie M.
    Xie, Weijia
    Bergman, Richard N.
    Boehnke, Michael
    el Bouazzaoui, Fatiha
    Collins, Francis S.
    Dunn, Sandra H.
    Dupuis, Josee
    Forouhi, Nita G.
    Gillson, Christopher
    Hattersley, Andrew T.
    Hong, Jaeyoung
    Kaehoenen, Mika
    Kuusisto, Johanna
    Kedenko, Lyudmyla
    Kronenberg, Florian
    Doria, Alessandro
    Assimes, Themistocles L.
    Ferrannini, Ele
    Hansen, Torben
    Hao, Ke
    Haering, Hans
    Knowles, Joshua W.
    Lindgren, Cecilia M.
    Nolan, John J.
    Paananen, Jussi
    Pedersen, Oluf
    Quertermous, Thomas
    Smith, Ulf
    Lehtimaeki, Terho
    Liu, Ching-Ti
    Loos, Ruth J. F.
    McCarthy, Mark I.
    Morris, Andrew D.
    Vasan, Ramachandran S.
    Spector, Tim D.
    Teslovich, Tanya M.
    Tuomilehto, Jaakko
    van Dijk, Ko Willems
    Viikari, Jorma S.
    Zhu, Na
    Langenberg, Claudia
    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.
    Semple, Robert K.
    Sinaiko, Alan R.
    Palmer, Colin N. A.
    Walker, Mark
    Lam, Karen S. L.
    Paulweber, Bernhard
    Mohlke, Karen L.
    van Duijn, Cornelia
    Raitakari, Olli T.
    Bidulescu, Aurelian
    Wareham, Nick J.
    Laakso, Markku
    Waterworth, Dawn M.
    Lawlor, Debbie A.
    Meigs, James B.
    Richards, J. Brent
    Frayling, Timothy M.
    Mendelian Randomization Studies Do Not Support a Causal Role for Reduced Circulating Adiponectin Levels in Insulin Resistance and Type 2 Diabetes2013In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 62, no 10, p. 3589-3598Article in journal (Refereed)
    Abstract [en]

    Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics-based genetic risk scores to test the associations with gold-standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 case subjects and 64,731 control subjects). In conventional regression analyses, a 1-SD decrease in adiponectin levels was correlated with a 0.31-SD (95% CI 0.26-0.35) increase in fasting insulin, a 0.34-SD (0.30-0.38) decrease in insulin sensitivity, and a type 2 diabetes odds ratio (OR) of 1.75 (1.47-2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD; 95% CI -0.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (-0.20 SD; 95% CI -0.38 to -0.02; N = 1,860), and no evidence of a relationship with type 2 diabetes (OR 0.94; 95% CI 0.75-1.19; N = 2,777 case subjects and 13,011 control subjects). Using the ADIPOQ summary statistics genetic risk scores, we found no evidence of an association between adiponectin-lowering alleles and insulin sensitivity (effect per weighted adiponectin-lowering allele: -0.03 SD; 95% CI -0.07 to 0.01; N = 2,969) or type 2 diabetes (OR per weighted adiponectin-lowering allele: 0.99; 95% CI 0.95-1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of type 2 diabetes.

  • 306.
    Yang, Jian
    et al.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia..
    Bakshi, Andrew
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Zhu, Zhihong
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Hemani, Gibran
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Bristol, Sch Social & Community Med, IEU, MRC, Bristol, Avon, England..
    Vinkhuyzen, Anna A. E.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Lee, Sang Hong
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ New England, Sch Environm & Rural Sci, Armidale, NSW, Australia..
    Robinson, Matthew R.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Perry, John R. B.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Inst Metab Sci, Cambridge, England..
    Nolte, Ilja M.
    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..
    Snieder, Harold
    Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands..
    Esko, Tonu
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Boston Childrens Hosp, Div Endocrinol, Cambridge, MA USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Harvard Univ, Sch Med, Dept Genet, Boston, MA USA..
    Milani, Lili
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    Maegi, Reedik
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.;Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden..
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    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..
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.;Univ Cambridge, Dept Haematol, Cambridge, England..
    Keller, Matthew C.
    Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.;Univ Colorado, Inst Behav Genet, Boulder, CO 80309 USA..
    Wray, Naomi R.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Goddard, Michael E.
    Univ Melbourne, Fac Vet & Agr Sci, Parkville, Vic 3052, Australia.;Jobs Transport & Resources, Dept Econ Dev, Biosci Res Div, Bundoora, Vic, Australia..
    Visscher, Peter M.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia..
    Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index2015In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, no 10, p. 1114-1120Article in journal (Refereed)
    Abstract [en]

    We propose a method (GREML-LDMS) to estimate heritability for human complex traits in unrelated individuals using whole-genome sequencing data. We demonstrate using simulations based on whole-genome sequencing data that similar to 97% and similar to 68% of variation at common and rare variants, respectively, can be captured by imputation. Using the GREML-LDMS method, we estimate from 44,126 unrelated individuals that all similar to 17 million imputed variants explain 56% (standard error (s.e.) = 2.3%) of variance for height and 27% (s.e. = 2.5%) of variance for body mass index (BMI), and we find evidence that height- and BMI-associated variants have been under natural selection. Considering the imperfect tagging of imputation and potential overestimation of heritability from previous family-based studies, heritability is likely to be 60-70% for height and 30-40% for BMI. Therefore, the missing heritability is small for both traits. For further discovery of genes associated with complex traits, a study design with SNP arrays followed by imputation is more cost-effective than whole-genome sequencing at current prices.

  • 307. Yang, Jian
    et al.
    Bakshi, Andrew
    Zhu, Zhihong
    Hemani, Gibran
    Vinkhuyzen, Anna A E
    Nolte, Ilja M
    van Vliet-Ostaptchouk, Jana V
    Snieder, Harold
    Esko, Tonu
    Milani, Lili
    Mägi, Reedik
    Metspalu, Andres
    Hamsten, Anders
    Magnusson, Patrik K E
    Pedersen, Nancy L
    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.
    Visscher, Peter M
    Genome-wide genetic homogeneity between sexes and populations for human height and body mass index2015In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 24, no 25, p. 7445-7449Article in journal (Refereed)
    Abstract [en]

    Sex-specific genetic effects have been proposed to be an important source of variation for human complex traits. Here we use two distinct genome-wide methods to estimate the autosomal genetic correlation (rg) between men and women for human height and body mass index (BMI), using individual-level (n = ∼44 000) and summary-level (n = ∼133 000) data from genome-wide association studies. Results are consistent and show that the between-sex genetic correlation is not significantly different from unity for both traits. In contrast, we find evidence of genetic heterogeneity between sexes for waist-hip ratio (rg = ∼0.7) and between populations for BMI (rg = ∼0.9 between Europe and the USA) but not for height. The lack of evidence for substantial genetic heterogeneity for body size is consistent with empirical findings across traits and species.

  • 308.
    Yao, Chen
    et al.
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
    Chen, George
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
    Song, Ci
    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, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA; NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
    Keefe, Joshua
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
    Mendelson, Michael
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA;Boston Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA.
    Huan, Tianxiao
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
    Sun, Benjamin B.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.
    Laser, Annika
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany.
    Maranville, Joseph C.
    Merck & Co Inc, MRL, Kenilworth, NJ 07033 USA.
    Wu, Hongsheng
    Wentworth Inst Technol, Comp Sci & Networking, Boston, MA 02115 USA.
    Ho, Jennifer E.
    Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
    Courchesne, Paul
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
    Lyass, Asya
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;Boston Univ, Dept Math & Stat, Boston, MA 02115 USA.
    Larson, Martin G.
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
    Gieger, Christian
    German Ctr Diabet Res DZD, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany.
    Graumann, Johannes
    WG Kerckhoff Inst, Max Planck Inst Heart & Lung Res, Sci Serv Grp Biomol Mass Spectrometry, Ludwigstr 43, D-61231 Bad Nauheim, Germany.
    Johnson, Andrew D.
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
    Danesh, John
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;Boston Univ, Dept Math & Stat, Boston, MA 02115 USA.
    Runz, Heiko
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
    Hwang, Shih-Jen
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany.
    Liu, Chunyu
    Butterworth, Adam S.
    Wellcome Trust Sanger Inst, Dept Human Genet, Wellcome Trust Genome Campus, Cambridge CB10 1RQ, England;Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gom, Cambridge CB1 8RN, England;Addenbrookes Hosp, British Heart Fdn, Cambridge Ctr Excellence, Div Cardiovasc Med, Cambridge CB2 0QQ, England.
    Suhre, Karsten
    Weill Cornell Med Qatar, Dept Physiol & Biophys, PO 24144, Doha, Qatar;Merck & Co Inc, MRL, Kenilworth, NJ 07033 USA.
    Levy, Daniel
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;NHLBI, Populat Sci Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
    Genome-wide mapping of plasma protein QTLs identifies putatively causal genes and pathways for cardiovascular disease2018In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 3268Article in journal (Refereed)
    Abstract [en]

    Identifying genetic variants associated with circulating protein concentrations (protein quantitative trait loci; pQTLs) and integrating them with variants from genome-wide association studies (GWAS) may illuminate the proteome's causal role in disease and bridge a knowledge gap regarding SNP-disease associations. We provide the results of GWAS of 71 high-value cardiovascular disease proteins in 6861 Framingham Heart Study participants and independent external replication. We report the mapping of over 16,000 pQTL variants and their functional relevance. We provide an integrated plasma protein-QTL database. Thirteen proteins harbor pQTL variants that match coronary disease-risk variants from GWAS or test causal for coronary disease by Mendelian randomization. Eight of these proteins predict new-onset cardiovascular disease events in Framingham participants. We demonstrate that identifying pQTLs, integrating them with GWAS results, employing Mendelian randomization, and prospectively testing protein-trait associations holds potential for elucidating causal genes, proteins, and pathways for cardiovascular disease and may identify targets for its prevention and treatment.

  • 309. Yin, Li
    et al.
    Lensmar, Catarina
    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.
    Back, Magnus
    Differential association of chronic obstructive pulmonary disease with myocardial infarction and ischemic stroke in a nation-wide cohort2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 173, no 3, p. 601-603Article in journal (Other academic)
  • 310.
    Yi-Ting, Lin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Family Med, Kaohsiung, Taiwan.
    Chou, Mei-Chuan
    Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Neurol, Kaohsiung, Taiwan;Kaohsiung Med Univ, Kaohsiung Municipal Ta Tung Hosp, Dept Neurol, Kaohsiung, Taiwan.
    Wu, Shyh-Jong
    Kaohsiung Med Univ, Dept Med Lab Sci & Biotechnol, Kaohsiung, Taiwan.
    Yang, Yuan-Han
    Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Dept Neurol, Kaohsiung, Taiwan;Kaohsiung Med Univ, Kaohsiung Municipal Ta Tung Hosp, Dept Neurol, Kaohsiung, Taiwan;Kaohsiung Med Univ, Fac Med, Dept Neurol, Kaohsiung, Taiwan;Kaohsiung Med Univ, Fac Med, Masters Program Neurol, Kaohsiung, Taiwan;Kaohsiung Med Univ, Neurosci Res Ctr, Kaohsiung, Taiwan.
    Galantamine plasma concentration and cognitive response in Alzheimer's disease2019In: PeerJ, ISSN 2167-8359, E-ISSN 2167-8359, Vol. 7, article id e6887Article in journal (Refereed)
    Abstract [en]

    Background

    Galantamine has been approved for the treatment of Alzheimer's disease (AD). However, there are few studies which have reported the association between cognitive responses and galantamine plasma concentration. The aim of this study was to determine the correlation between galantamine plasma concentration and the subsequent cognitive response following treatment in AD patients.

    Methods

    ADsufferers who continuously took 8 mg/d galantamine for at least 6 months without previous exposure to other kinds of AChEI such as donepezil, rivastigmine, or memantine were included in this cohort study. The assessments included the Mini Mental Status Examination (MMSE), Clinical Dementia Rating Scale (CDR) and the Cognitive Assessment Screening Instrument (CASI). Each subdomain of the CASI assessment was conducted at baseline and after 6 months of galantamine. The plasma concentrations of galantamine were measured by capillary electrophoresis after 6 months of the treatment. Logistic regression was performed to adjust for age, gender, apolipoprotein E epsilon 4 genotype status, and baseline score to investigate the association between galantamine plasma concentrations and the cognitive response.

    Results

    The total sample consisted of 33 clinically diagnosed AD patients taking galantamine 8 mg/d for 6 months. There was no linear correlation between galantamine concentration and cognitive response in patients. However, 22 patients were responsive to the treatment in the long-term memory domain. In CASI subset domain, concentration improved during the 6 months follow up.

    Conclusions

    In the limited samples study, galantamine mostly benefitted the cognitive domain of long-term memory. The benefits were not related to the galantamine plasma concentration. Objective intra-individual evaluation of therapeutic response should be encouraged.

  • 311.
    Yi-Ting, Lin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ingelsson, Erik
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Arnlov, Johan
    Karolinska Inst, Dept Neurobiol, Div Family Med & Primary Care, Stockholm, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Engström, Gunnar
    Lund Univ, Dept Clin Sci, Cardiovasc Epidemiol, Lund, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Use of Proteomics to Investigate Blood Pressure Progress in the Elderly2018In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, p. E115-E115Article in journal (Other academic)
  • 312.
    Zanetti, Daniela
    et al.
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, 300 Pasteur Dr,Mail Code 5406, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Rao, Abhiram
    Stanford Univ, Dept Bioengn, 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.
    Assimes, Themistocles L.
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, 300 Pasteur Dr,Mail Code 5406, Stanford, CA 94305 USA.
    Montgomery, Stephen B.
    Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA.
    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, 300 Pasteur Dr,Mail Code 5406, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Identification of 22 novel loci associated with urinary biomarkers of albumin, sodium, and potassium excretion2019In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 95, no 5, p. 1197-1208Article in journal (Refereed)
    Abstract [en]

    Urine biomarkers reflecting kidney function and handling of dietary sodium and potassium are strongly associated with several common diseases including chronic kidney disease, cardiovascular disease, and diabetes mellitus. Knowledge about the genetic determinants of these biomarkers may shed light on pathophysiological mechanisms underlying the development of these diseases. We performed genome-wide association studies of urinary albumin: creatinine ratio (UACR), urinary potassium: creatinine ratio (UK/UCr), urinary sodium: creatinine ratio (UNa/UCr) and urinary sodium: potassium ratio (UNa/UK) in up to 218,450 (discovery) and 109,166 (replication) unrelated individuals of European ancestry from the UK Biobank. Further, we explored genetic correlations, tissue-specific gene expression, and possible genes implicated in the regulation of these biomarkers. After replication, we identified 19 genome-wide significant independent loci associated with UACR, 6 each with UK/UCr and UNa/UCr, and 4 with UNa/UK. In addition to 22 novel associations, we confirmed several established associations, including between the CUBN locus and microalbuminuria. We detected high pairwise genetic correlation across the urinary biomarkers, and between their levels and several physiological measurements. We highlight GIPR, a potential diabetes drug target, as possibly implicated in the genetic control of urinary potassium excretion, and NRBP1, a locus associated with gout, as plausibly involved in sodium and albumin excretion. Overall, we identified 22 novel genome-wide significant associations with urinary biomarkers and confirmed several previously established associations, providing new insights into the genetic basis of these traits and their connection to chronic diseases.

  • 313.
    Zanetti, Daniela
    et al.
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, 300 Pasteur Dr,Mail Code 5773, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Tikkanen, Emmi
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, 300 Pasteur Dr,Mail Code 5773, 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. Stanford University School of Medicine, CA..
    Priest, James R.
    Stanford Univ, Sch Med, Div Cardiol, Dept Pediat, Stanford, CA 94305 USA.
    Burgess, Stephen
    Univ Cambridge, Biostat Unit, MRC, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    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, 300 Pasteur Dr,Mail Code 5773, Stanford, CA 94305 USA;Stanford Univ, Sch Med, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Birthweight, Type 2 Diabetes Mellitus, and Cardiovascular Disease Addressing the Barker Hypothesis With Mendelian Randomization2018In: CIRCULATION-GENOMIC AND PRECISION MEDICINE, ISSN 2574-8300, Vol. 11, no 6, article id UNSP e002054Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Low birthweight has been associated with a higher risk of hypertension, type 2 diabetes mellitus (T2D), and cardiovascular disease. The Barker hypothesis posits that intrauterine growth restriction resulting in lower birthweight is causal for these diseases, but causality is difficult to infer from observational studies. METHODS: We performed regression analyses to assess associations of birthweight with cardiovascular disease and T2D in 237 631 individuals from the UK Biobank. Further, we assessed the causal relationship of such associations using Mendelian randomization. RESULTS: In the observational analyses, birthweight showed inverse associations with systolic and diastolic blood pressure (beta, -0.83 and -0.26; per raw unit in outcomes and SD change in birthweight; 95% confidence interval [CI], -0.90 to -0.75 and -0.31 to -0.22, respectively), T2D (odds ratio, 0.83; 95% CI, 0.79-0.87), lipid-lowering treatment (odds ratio, 0.84; 95% CI, 0.81-0.86), and coronary artery disease (hazard ratio, 0.85; 95% CI, 0.78-0.94), whereas the associations with adult body mass index and body fat (beta, 0.04 and 0.02; per SD change in outcomes and birthweight; 95% CI, 0.03-0.04 and 0.01-0.02, respectively) were positive. The Mendelian randomization analyses indicated inverse causal associations of birthweight with low-density lipoprotein cholesterol, 2-hour glucose, coronary artery disease, and T2D and positive causal association with body mass index but no associations with blood pressure. CONCLUSIONS: Our study indicates that lower birthweight, used as a proxy for intrauterine growth retardation, is causally related with increased susceptibility to coronary artery disease and T2D. This causal relationship is not mediated by adult obesity or hypertension.

  • 314.
    Zhou, Ang
    et al.
    Univ South Australia, Australian Ctr Precis Hlth, Adelaide, SA, Australia.
    Taylor, Amy E.
    Univ Bristol, MRC Integrat Epidemiol Unit IEU, Bristol, Avon, England;Univ Bristol, UKCTAS, Bristol, Avon, England;Univ Bristol, Sch Expt Psychol, Bristol, Avon, England.
    Karhunen, Ville
    Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland;Oulu Univ Hosp, Oulu, Finland.
    Zhan, Yiqiang
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Rovio, Suvi P.
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
    Lahti, Jari
    Helsinki Collegium Adv Studies, Helsinki, Finland;Univ Helsinki, Dept Psychol & Logoped, Fac Med, Helsinki, Finland.
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lyall, Donald M.
    Univ Glasgow, Inst Hlth & Wellbeing, Glasgow, Lanark, Scotland.
    Auvinen, Juha
    Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland;Oulu Univ Hosp, Unit Primary Hlth Care, Oulu, Finland.
    Lehtimaki, Terho
    Univ Tampere, Fac Med & Life Sci, Fimlab Labs, Dept Clin Chem, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland.
    Kahonen, Mika
    Univ Tampere, Dept Clin Physiol, Tampere Univ Hosp, Tampere, Finland;Univ Tampere, Fac Med & Life Sci, Tampere, Finland.
    Hutri-Kahonen, Nina
    Univ Tampere, Fac Med & Life Sci, Tampere, Finland;Univ Tampere, Tampere Univ Hosp, Dept Pediat, Tampere, Finland.
    Perala, Mia Maria
    Natl Inst Hlth & Welf, Dept Publ Hlth Solut, Helsinki, Finland.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mahajan, Anubha
    Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford OX3 7BN, England.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Power, Chris
    UCL Great Ormond St Inst Child Hlth, Populat Policy & Practice, London WC1N 1EH, England.
    Eriksson, Johan G.
    Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland;Folkhalsan Res Ctr, Helsinki, Finland.
    Raitakari, Olli T.
    Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland;Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland.
    Hagg, Sara
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Veijola, Juha
    Univ Oulu, Dept Psychiat, Res Unit Clin Neurosci, Oulu, Finland;Univ Hosp Oulu, Dept Psychiat, Oulu, Finland.
    Jarvelin, Marjo-Riitta
    Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland;Oulu Univ Hosp, Unit Primary Hlth Care, Oulu, Finland;Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London, England;Univ Oulu, Bioctr Oulu, Oulu, Finland.
    Munafo, Marcus R.
    Univ Bristol, MRC Integrat Epidemiol Unit IEU, Bristol, Avon, England;Univ Bristol, UKCTAS, Bristol, Avon, England;Univ Bristol, Sch Expt Psychol, Bristol, Avon, England.
    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, Div Cardiovasc Med, Dept Med, Sch Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Llewellyn, David J.
    Univ Exeter, Med Sch, Exeter, Devon, England.
    Hypponen, Elina
    Univ South Australia, Australian Ctr Precis Hlth, Adelaide, SA, Australia;UCL Great Ormond St Inst Child Hlth, Populat Policy & Practice, London WC1N 1EH, England;South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.
    Habitual coffee consumption and cognitive function: a Mendelian randomization meta-analysis in up to 415,530 participants2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 7526Article in journal (Refereed)
    Abstract [en]

    Coffee's long-term effect on cognitive function remains unclear with studies suggesting both benefits and adverse effects. We used Mendelian randomization to investigate the causal relationship between habitual coffee consumption and cognitive function in mid-to later life. This included up to 415,530 participants and 300,760 coffee drinkers from 10 meta-analysed European ancestry cohorts. In each cohort, composite cognitive scores that capture global cognition and memory were computed using available tests. A genetic score derived using CYP1A1/2 (rs2472297) and AHR (rs6968865) was chosen as a proxy for habitual coffee consumption. Null associations were observed when examining the associations of the genetic score with global and memory cognition (beta = -0.0007, 95% C.I. -0.009 to 0.008, P = 0.87; beta = -0.001, 95% C.I. -0.005 to 0.002, P = 0.51, respectively), with high consistency between studies (P-heterogeneity > 0.4 for both). Domain specific analyses using available cognitive measures in the UK Biobank also did not support effects by habitual coffee intake for reaction time, pairs matching, reasoning or prospective memory (P >= 0.05 for all). Despite the power to detect very small effects, our meta-analysis provided no evidence for causal long-term effects of habitual coffee consumption on global cognition or memory.

  • 315.
    Zillikens, M. Carola
    et al.
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NCI, NL-2593 Leiden, Netherlands..
    Demissie, Serkalem
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Hsu, Yi-Hsiang
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Harvard Sch Publ Hlth, Mol & Integrat Physiol Sci Program, Boston, MA 02115 USA..
    Yerges-Armstrong, Laura M.
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA..
    Chou, Wen-Chi
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst, Cambridge, MA 02142 USA..
    Stolk, Lisette
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NCI, NL-2593 Leiden, Netherlands..
    Livshits, Gregory
    Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-6997801 Tel Aviv, Israel.;Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London WC2R 2LS, England..
    Broer, Linda
    Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Johnson, Toby
    Univ Lausanne, Dept Med Genet, CH-1011 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Inst Social & Prevent Med, Ctr Hosp Univ CHUV, CH-1010 Lausanne, Switzerland..
    Koller, Daniel L.
    Indiana Univ, Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA..
    Kutalik, Zoltyn
    Univ Lausanne, Dept Med Genet, CH-1011 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Inst Social & Prevent Med, Ctr Hosp Univ CHUV, CH-1010 Lausanne, Switzerland..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England..
    Malkin, Ida
    Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-6997801 Tel Aviv, Israel..
    Ried, Janina S.
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany..
    Smith, Albert V.
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland..
    Thorleifsson, Gudmar
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland..
    Vandenput, Liesbeth
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England..
    Zhang, Weihua
    Imperial Coll, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England.;Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England..
    Aghdassi, Ali
    Ernst Moritz Arndt Univ Greifswald, Dept Med A, D-17489 Greifswald, Germany..
    Akesson, Kristina
    Lund Univ, Dept Clin Sci, S-22362 Malmo, Sweden.;Skane Univ Hosp, Dept Orthoped, S-20502 Malmo, Sweden..
    Amin, Najaf
    Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Baier, Leslie J.
    NIH, Phoenix Epidemiol & Clin Res Branch, Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ 85014 USA..
    Barroso, Ines
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Saffron Walden CB10 1SA, Essex, England.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Inst Met Sci, Cambridge CB2 OQQ, England.;Univ Cambridge, Addenbrookes Hosp, Inst Met Sci, Metab Res Labs, Cambridge CB2 OQQ, England..
    Bennett, David A.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA..
    Bertram, Lars
    Univ Lubeck, Lubeck Interdisciplinary Platform Genome Analyt, Inst Neurogenet & Expt & Integrat Gen, D-23562 Lubeck, Germany.;Imperial Coll London, Fac Med, Sch Publ Hlth, London W6 8RP, England..
    Biffar, Rainer
    Ernst Moritz Arndt Univ Greifswald, Ctr Oral Hlth, Dept Prosthet Dent Gerodontol & Biomat, D-17489 Greifswald, Germany..
    Bochud, Murielle
    Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Inst Social & Prevent Med, Ctr Hosp Univ CHUV, CH-1010 Lausanne, Switzerland..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Borecki, Ingrid B.
    Washington Univ, Div Stat Gen, Dept Genet, Sch Med, St Louis, MO 63110 USA.;Washington Univ, Div Biostat, Sch Med, St Louis, MO 63110 USA..
    Buchman, Aron S.
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA..
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Campbell, Harry
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Obanda, Natalia Campos
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands..
    Cauley, Jane A.
    Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA..
    Cawthon, Peggy M.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA..
    Cederberg, Henna
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Chen, Zhao
    Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85714 USA..
    Cho, Nam H.
    Ajou Univ, Sch Med, Dept Prevent Med, Suwon 16499, South Korea..
    Choi, Hyung Jin
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 03080, South Korea.;Chungbuk Natl Univ Hosp, Dept Internal Med, Cheongju, South Korea..
    Claussnitzer, Melina
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Broad Inst, Cambridge, MA 02142 USA.;MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 USA.;Tech Univ Munich, Inst Human Genet, MRI, D-81675 Munich, Germany.;Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA..
    Collins, Francis
    Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Cummings, Steven R.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA..
    De Jager, Philip L.
    Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens Hosp, Dept Neurol, Program Translat NeuroPsychiatr Genom, Boston, MA 02115 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Demuth, Ilja
    Charite, Res Grp Geriatr, Berlin Aging Study 2, D-13353 Berlin, Germany.;Charite, Inst Med & Human Genet, D-13353 Berlin, Germany..
    Dhonukshe-Rutten, Rosalie A. M.
    Wageningen Univ, Dept Human Nutr, POB 17, NL-6700 AA Wageningen, Netherlands..
    Diatchenko, Luda
    McGill Univ, Alan Edwards Ctr Res Pain, Montreal H3A 0G1, PQ, Canada.;Univ N Carolina, Sch Dent, Reg Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA..
    Eiriksdottir, Gudny
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland..
    Enneman, Anke W.
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands..
    Erdos, Mike
    Natl Human Genome Res Inst, Med Genom & Metab Genet Branch, Bethesda, MD 20892 USA..
    Eriksson, Johan G.
    Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki 00014, Finland.;Univ Helsinki, Cent Hosp, Unity Gen Practice, Helsinki 00014, Finland.;Folkhalsan Res Ctr, Helsinki 00250, Finland.;Vasa Cent Hosp, Vaasa 65130, Finland.;Nat Inst Hlth & Welf, Helsinki 00271, Finland..
    Eriksson, Joel
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Estrada, Karol
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Evans, Daniel S.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA..
    Feitosa, Mary F.
    Washington Univ, Div Stat Gen, Dept Genet, Sch Med, St Louis, MO 63110 USA..
    Fu, Mao
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA..
    Garcia, Melissa
    Natl Inst Aging, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA..
    Gieger, Christian
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Inst Genet Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany..
    Girke, Thomas
    Univ Calif Riverside, Inst Integrat Genome Biol, Dept Bot & Plant Sci, Riverside, CA 92521 USA.;Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA..
    Glazer, Nicole L.
    Boston Univ, Sch Med & Publ Hlth, Dept Med, Boston, MA 02118 USA.;Boston Univ, Sch Med & Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA..
    Grallert, Harald
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Univ Calif Riverside, Dept Bot & Plant Sci, Riverside, CA 92521 USA.;German Ctr Diabet Res DZD, Neuherberg, Germany.;Helmholtz Zentrum Munchen, CCG Type Diabet 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, CCG Nutrigen & Type Diabet 2, D-85764 Neuherberg, Germany..
    Grewal, Jagvir
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Imperial Coll London, Natl Heart & Lung Inst, London SW3 6LY, England..
    Han, Bok-Ghee
    Osong Hlth Technol Adm Complex, Ctr Genome Sci, Natl Inst Hlth, Chungcheongbuk Do 28159, South Korea..
    Hanson, Robert L.
    NIH, Phoenix Epidemiol & Clin Res Branch, Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ 85014 USA..
    Hayward, Caroline
    Univ Edinburgh, IGMM, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland..
    Hofman, Albert
    NCHA, NCI, NL-2593 Leiden, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Hoffman, Eric P.
    SUNY Binghamton, Dept Pharmaceut Sci, Binghamton, NY 13902 USA..
    Homuth, Georg
    Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Gen, D-17487 Greifswald, Germany..
    Hsueh, Wen-Chi
    NIH, Phoenix Epidemiol & Clin Res Branch, Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ 85014 USA..
    Hubal, Monica J.
    George Washington Univ, Dept Exercise & Nutr Sci, Washington, DC 20052 USA.;Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20052 USA..
    Hubbard, Alan
    Univ Calif Berkeley, Div Biostat, Sch Publ Hlth, Berkeley, CA 94720 USA..
    Huffman, Kim M.
    Duke Univ, Sch Med, Div Rheumatol, Dept Med,Duke Mol Physiol Inst, Durham, NC 27710 USA..
    Husted, Lise B.
    Aarhus Univ Hosp, Endocrinol & Internal Med, DK-8000 Aarhus, Denmark..
    Illig, Thomas
    Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Hannover Med Sch, Dept Human Genet, D-30625 Hannover, Germany.;Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany..
    Ingelsson, Erik
    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..
    Ittermann, Till
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17489 Greifswald, Germany..
    Jansson, John-Olov
    Univ Gothenburg, Dept Physiol, Inst Neurosci & Physiol, Sahlgrenska Acad, SE-40530 Gothenburg, Sweden..
    Jordan, Joanne M.
    Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC 27517 USA..
    Jula, Antti
    Nat Inst Hlth & Welf, Helsinki 00271, Finland..
    Karlsson, Magnus
    Lund Univ, Dept Clin Sci & Orthopaed, Skane Univ Hosp SUS, S-22362 Malmo, Sweden..
    Khaw, Kay-Tee
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England..
    Kilpainen, Tuomas O.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England.;Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Sect Metab Genet, DK-2100 Copenhagen, Denmark.;Icahn Sch Med Mt Sinai, Dept Environm Med & Publ Hlth, New York, NY 10029 USA..
    Klopp, Norman
    Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany.;Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany..
    Kloth, Jacqueline S. L.
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands..
    Koistinen, Heikki A.
    Univ Helsinki, Dept Med, Helsinki 00029, Finland.;Helsinki Univ Cent Hosp, Helsinki 00029, Finland.;Univ Helsinki, Abdominal Ctr, Endocrinol, Helsinki 00029, Finland.;Natl Inst Hlth & Welf, Dept Hlth, Helsinki 00271, Finland.;Minerva Fdn, Helsinki 00290, Finland..
    Kraus, William E.
    Duke Univ, Sch Med, Div Cardiol, Dept Med,Duke Mol Physiol Inst, Durham, NC 27710 USA..
    Kritchevsky, Stephen
    Sticht Ctr Aging, Wake Forest Sch Med, Winston Salem, NC 27157 USA..
    Kuulasmaa, Teemu
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Kuusisto, Johanna
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Laakso, Markku
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Lahti, Jari
    Univ Helsinki, Inst Behav Sci, FI-00014 Helsinki, Finland..
    Lang, Thomas
    Univ Calif San Francisco, San Francisco, CA 94143 USA..
    Langdahl, Bente L.
    Aarhus Univ Hosp, Endocrinol & Internal Med, DK-8000 Aarhus, Denmark..
    Launer, Lenore J.
    Natl Inst Aging, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA..
    Lee, Jong-Young
    Osong Hlth Technol Adm Complex, Ctr Genome Sci, Natl Inst Hlth, Chungcheongbuk Do 28159, South Korea..
    Lerch, Markus M.
    Ernst Moritz Arndt Univ Greifswald, Dept Med A, D-17489 Greifswald, Germany..
    Lewis, Joshua R.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.;Univ Sydney, Ctr Kidney Res, Sch Publ Hlth, Sydney, NSW 2006, Australia..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala Univ, Dept Med Sci, S-75185 Uppsala, Sweden..
    Lindgren, Cecilia
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Liu, Yongmei
    Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC 27517 USA..
    Liu, Tian
    Max Planck Inst Mol Genet, D-14195 Berlin, Germany.;Max Planck Inst Human Dev, D-14195 Berlin, Germany..
    Liu, Youfang
    Univ N Carolina, Thurston Arthrit Res Ctr, Chapel Hill, NC 27517 USA..
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Lorentzon, Mattias
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Luben, Robert N.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England..
    Maixner, William
    Univ N Carolina, Sch Dent, Reg Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA..
    McGuigan, Fiona E.
    Lund Univ, Dept Clin Sci, S-22362 Malmo, Sweden..
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, MRI, D-81675 Munich, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, D-85764 Neuherberg, Germany..
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Mellstrom, Dan
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Melov, Simon
    Buck Inst Res Aging, Novato, CA 94945 USA.;Univ Southern Calif, Leonard Davis Sch Gerontol, Los Angeles, CA 90089 USA..
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Mitchell, Braxton D.
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA.;Baltimore Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Liverpool, Inst Tradit Med, Liverpool L69 3BX, Merseyside, England..
    Mosekilde, Leif
    Aarhus Univ Hosp, Endocrinol & Internal Med, DK-8000 Aarhus, Denmark..
    Newman, Anne
    Univ Pittsburgh, Ctr Aging & Populat Hlth, Pittsburgh, PA 15261 USA..
    Nielson, Carrie M.
    Oregon Hlth & Sci Univ, Portland, OR 97239 USA..
    O'Connell, Jeffrey R.
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA..
    Oostra, Ben A.
    Erasmus MC, Dept Clin Genet, NL-300 CA Rotterdam, Netherlands.;Ctr Med Syst Biol & Netherlands Consortium Hlth A, RC-2300 Leiden, Netherlands..
    Orwoll, Eric S.
    Oregon Hlth & Sci Univ, Portland, OR 97239 USA..
    Palotie, Aarno
    Harvard Med Sch, Boston, MA 02115 USA.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland.;Univ Helsinki, Dept Med Genet, FI-00014 Helsinki, Finland.;Univ Cent Hosp, FI-00014 Helsinki, Finland..
    Parker, Stephan
    Univ Michigan, Human Genet & Computat Med & Bioinformat, Ann Arbor, MI 48109 USA..
    Peacock, Munro
    Indiana Univ, Dept Med, Sch Med, Indianapolis, IN 46202 USA..
    Perola, Markus
    Nat Inst Hlth & Welf, Helsinki 00271, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland.;Univ Helsinki, Diabet & Obes Res Program, FI-00014 Helsinki, Finland.;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Peters, Annette
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, Rese Unit Mol Epidemiol, German Res Ctr Environm Hlth, D-85764 Neuherberg, Germany..
    Polasek, Ozren
    Univ Split, Fac Med, Dept Publ Hlth, Split 21000, Croatia..
    Prince, Richard L.
    Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia.;Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Perth, WA 6009, Australia..
    Raikkonen, Katri
    Univ Helsinki, Inst Behav Sci, FI-00014 Helsinki, Finland..
    Ralston, Stuart H.
    Western Gen Hosp, Mol Med Ctr, MRC Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Ripatti, Samuli
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland.;Univ Helsinki, Hjelt Inst, Helsinki, Finland.;Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England..
    Robbins, John A.
    Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA..
    Rotter, Jerome I.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA..
    Rudan, Igor
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Salomaa, Veikko
    Nat Inst Hlth & Welf, Helsinki 00271, Finland..
    Satterfield, Suzanne
    Univ Tennessee, Dept Prevent Med, Hlth Sci Ctr, Memphis, TN 38163 USA..
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Inst Genom & Multiscale Biol, New York, NY 10029 USA..
    Schipf, Sabine
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17489 Greifswald, Germany..
    Scott, Laura
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Sehmi, Joban
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Imperial Coll London, Natl Heart & Lung Inst, London SW3 6LY, England..
    Shen, Jian
    Oregon Hlth & Sci Univ, Portland, OR 97239 USA..
    Shin, Chan Soo
    Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 03080, South Korea..
    Sigurdsson, Gunnar
    Natl Univ Hosp Iceland, Landspitali, Dept Endocrinol & Metab, IS-101 Reykjavik, Iceland..
    Smith, Shad
    Duke Univ, Med Ctr, Ctr Translat Pain Med, Dept Anesthesiol, Durham, NC 27110 USA..
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, England..
    Stancakova, Alena
    Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, Kuopio 70210, Finland..
    Steinhagen-Thiessen, Elisabeth
    Charite, Res Grp Geriatr, Berlin Aging Study 2, D-13353 Berlin, Germany..
    Streeten, Elizabeth A.
    Univ Maryland, Program Personalized & Genom Med, Baltimore, MD 21201 USA.;Univ Maryland, Div Endocrinol Diabet & Nutr, Dept Med, Baltimore, MD 21201 USA.;Vet Adm Med Ctr, GRECC, Baltimore, MD 21201 USA..
    Styrkarsdottir, Unnur
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland..
    Swart, Karin M. A.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, BT-1081 Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, EMGO Inst, BT-1081 Amsterdam, Netherlands..
    Tan, Sian-Tsung
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Imperial Coll London, Natl Heart & Lung Inst, London SW3 6LY, England..
    Tarnopolsky, Mark A.
    McMaster Univ, Med Ctr, Dept Med, Hamilton, ON L8N 3Z5, Canada..
    Thompson, Patricia
    Stony Brook Sch Med, Dept Pathol, Stony Brook, NY 11794 USA..
    Thomson, Cynthia A.
    Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth, Tucson, AZ 85714 USA..
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland..
    Tikkanen, Emmi
    Nat Inst Hlth & Welf, Helsinki 00271, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland.;Western Gen Hosp, Mol Med Ctr, MRC Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Tranah, Gregory J.
    Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94107 USA..
    Tuomilehto, Jaakko
    Vasa Cent Hosp, Vaasa 65130, Finland.;Danube Univ Krems, Dept Neurosci & Prevent Med, A-3500 Krems, Austria.;King Abdulaziz Univ, Diabet Res Grp, Jeddah 12589, Saudi Arabia.;Dasman Diabet Inst, Dasman 15462, Kuwait..
    van Schoor, Natasja M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, BT-1081 Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, EMGO Inst, BT-1081 Amsterdam, Netherlands..
    Verma, Arjun
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England..
    Vollenweider, Peter
    CHU Vaudois, Dept Med & Internal Med, CH-1011 Lausanne, Switzerland..
    Voelzke, Henry
    Ernst Moritz Arndt Univ Greifswald, Inst Community Med, D-17489 Greifswald, Germany..
    Wactawski-Wende, Jean
    SUNY Buffalo, Univ Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY 14214 USA..
    Walker, Mark
    Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England..
    Weedon, Michael N.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter EX1 2LU, Devon, England..
    Welch, Ryan
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Wichman, H. -Erich
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, D-81377 Munich, Germany.;Tech Univ, Inst Med Stat & Epidemiol, D-81675 Munich, Germany..
    Widen, Elisabeth
    Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki 00251, Finland..
    Williams, Frances M. K.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London WC2R 2LS, England..
    Wilson, James F.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.;Univ Edinburgh, IGMM, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland..
    Wright, Nicole C.
    Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA..
    Xie, Weijia
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter EX1 2LU, Devon, England..
    Yu, Lei
    Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA..
    Zhou, Yanhua
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Chambers, John C.
    Imperial Coll, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England.;Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Royal Brompton & Harefield NHS Fdn Trust, NIHR Cardiovasc Biomed Res Unit, London SW3 6NP, England.;Imperial Coll, London SW3 6NP, England.;Imperial Coll Healthcare NHS Trust, London W2 1NY, England..
    Doring, Angela
    Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, D-85764 Neuherberg, Germany..
    van Duijn, Cornelia M.
    Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands.;Ctr Med Syst Biol & Netherlands Consortium Hlth A, RC-2300 Leiden, Netherlands..
    Econs, Michael J.
    Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA.;Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA..
    Gudnason, Vilmundur
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland..
    Kooner, Jaspal S.
    Ealing Hosp NHS Trust, Cardiol Dept, Middlesex UB1 3HW, England.;Imperial Coll London, Natl Heart & Lung Inst, London SW3 6LY, England.;Imperial Coll Healthcare NHS Trust, London W2 1NY, England..
    Psaty, Bruce M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Dept Med Hlth Serv, Seattle, WA 98101 USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, St Thomas Campus, London WC2R 2LS, England..
    Stefansson, Kari
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland..
    Rivadeneira, Fernando
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NCI, NL-2593 Leiden, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Uitterlinden, Andre G.
    Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NCI, NL-2593 Leiden, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England..
    Ossowski, Vicky
    NIH, Phoenix Epidemiol & Clin Res Branch, Natl Inst Diabet & Digest & Kidney Dis, Phoenix, AZ 85014 USA..
    Waterworth, Dawn
    GlaxoSmithKline, Med Genet, Philadelphia, PA 19112 USA..
    Loos, Ruth J. F.
    Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge Biomed Campus, Cambridge CB2 OQQ, England.;Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Inst Child Hlth & Dev, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Prevent Med, New York, NY 10029 USA..
    Karasik, David
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Bar Ilan Univ, Fac Med Galilee, IL-1311502 Safed, Israel..
    Harris, Tamara B.
    Natl Inst Aging, Intramural Res Program, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA..
    Ohlsson, Claes
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Internal Med, SE-40530 Gothenburg, Sweden..
    Kiel, Douglas P.
    Inst Aging Res, HebrewSenior Life, Roslindale, MA 02131 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA..
    Large meta-analysis of genome-wide association studies identifies five loci for lean body mass2017In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 80Article in journal (Refereed)
    Abstract [en]

    Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 x 10(-8)) or suggestively genome wide (p < 2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.

  • 316.
    Ärnlöv, Johan
    et al.
    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, Cardiovascular epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Carrero, J. J.
    Karolinska Inst, Stockholm, Sweden..
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stenemo, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Larsson, A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Carlsson, A. C.
    Karolinska Inst, Stockholm, Sweden..
    Discovery and replication of new risk markers for 5-year kidney function decline using a targeted multiplex proteomics chip2016Conference paper (Refereed)
  • 317.
    Ärnlöv, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ruge, Toralph
    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.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Serum endostatin and risk of mortality in the elderly: findings from 2 community-based cohorts2013In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 33, no 11, p. 2689-2695Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Experimental data imply that endostatin, a proteolytically cleaved fragment of collagen XVIII, could be involved in the development of cardiovascular disease and cancer. Prospective data concerning the relation between circulating endostatin and mortality are lacking. Accordingly, we aimed to study associations between circulating endostatin and mortality risk.

    APPROACH AND RESULTS:

    Serum endostatin was analyzed in 2 community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n=931; mean age, 70 years; median follow-up, 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=748; mean age, 77 years; median follow-up, 9.7 years). During follow-up, 90 participants died in PIVUS (1.28/100 person-years at risk), and 417 participants died in ULSAM (6.7/100 person-years at risk). In multivariable Cox regression models adjusted for age and established cardiovascular risk factors, 1 SD higher ln(serum endostatin level) was associated with a hazard ratio of mortality of 1.39 and 95% confidence interval, 1.26 to 1.53, on average in both cohorts. In the ULSAM cohort, serum endostatin was also associated with cardiovascular mortality (177 deaths; hazard ratio per SD of ln[endostatin] 1.45, 95% confidence interval [1.25-1.71]) and cancer mortality (115 deaths; hazard ratio per SD of ln[endostatin] 1.35, 95% confidence interval [1.10-1.66]).

    CONCLUSIONS:

    High serum endostatin was associated with increased mortality risk in 2 independent community-based cohorts of the elderly. Our observational data support the importance of extracellular matrix remodeling in the underlying pathophysiology of cardiovascular disease and cancer.

  • 318.
    Örtqvist, Anne K
    et al.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lundholm, Cecilia
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Fang, Fang
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 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.
    Almqvist, Catarina
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.; Unit of Pediatric Allergy and Pulmonology at Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
    Parental antibiotics and childhood asthma: a population-based study2017In: Journal of Allergy and Clinical Immunology: In Practice, ISSN 2213-2198, E-ISSN 2213-2201, Vol. 5, no 5, p. 1451-1454.e4, article id S2213-2198(17)30178-2Article in journal (Other academic)
    Abstract [en]

    In this population-based study on antibiotic treatment before, during, and after pregnancy, using paternal exposure as negative control, we confirm that associations between maternal antibiotic exposure and childhood asthma are partly explained by familial confounding such as genes and environment.

4567 301 - 318 of 318
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