Change search
Refine search result
1234567 151 - 200 of 330
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 151.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    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.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, P. Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Mixture effects of 30 environmental contaminants on incident metabolic syndrome: A prospective study2017In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 107, p. 8-15Article in journal (Refereed)
    Abstract [en]

    Background: Several cross-sectional studies have linked different environmental contaminants to the metabolic syndrome (MetS). However, mixture effects have not been investigated and no prospective studies exist regarding environmental contaminants and the MetS.

    Objectives: To study mixture effects of contaminants on the risk of incident MetS in a prospective fashion.

    Methods: Our sample consisted of 452 subjects from the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years) free from the MetS at baseline, being followed for 10 years. At baseline, 30 different environmental contaminants were measured; 6 polychlorinated biphenyls (PCBs), 3 organochlorine (OC) pesticides, one dioxin, one polybrominated diphenyl ether (all in plasma), 8 perfluoroalkyl substances (in plasma) and 11 metals (in whole blood). The MetS was defined by the ATPIII/NCEP criteria. Gradient boosted Classification and Regression Trees (CARTs) was used to evaluate potential synergistic and additive mixture effects on incident MetS.

    Results: During 10-year follow-up, 92 incident cases of the MetS occurred. PCB126, PCB170, hexachlorobenzene (HCB) and PCB118 levels were all associated with incident MetS in an additive fashion (OR 1.73 for a change from 10th to 90th percentile (95% CI 1.24-3.04) for PCB126, OR 0.63 (0.42-0.78) for PCB170, OR 1.44 (1.09-2.20) for HCB and OR 1.46 (1.13-2.43) for PCB118). No synergistic effects were found.

    Conclusion: A mixture of environmental contaminants, with PCB126, PCB170, HCB and PCB118 being the most important, showed associations with future development of the MetS in an additive fashion in this prospective study. Thus, mixture effects of environmental contaminants could contribute to the development of cardiometabolic derangements.

  • 152.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Univ Orebro, Orebro.
    Van Bavel, B.
    Univ Orebro, Orebro, Switzerland..
    Lind, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Circulating levels of perfluorinated compounds and left ventricular geometry2015In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 238, no 2, p. S93-S93Article in journal (Other academic)
  • 153.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Lindahl, Bertil
    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.
    Stenemo, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    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.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Discovery of New Risk Markers for Ischemic Stroke Using a Novel Targeted Proteomics Chip2015In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 46, no 12, p. 3340-3347Article in journal (Refereed)
    Abstract [en]

    Background and Purpose-Emerging technologies have made it possible to simultaneously evaluate a large number of circulating proteins as potential new stroke risk markers. Methods-We explored associations between 85 cardiovascular proteins, assessed by a proteomics chip, and incident ischemic stroke in 2 independent cohorts of elderly (Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS]: n=977; 50% women, mean age=70.1 years, 71 fatal/nonfatal ischemic stroke events during 10.0 years; and Uppsala Longitudinal Study in Adult Men [ULSAM]: n=720, mean age=77.5 years, 75 ischemic stroke events during 9.5 years). The proteomics chip uses 2 antibodies for each protein and a polymerase chain reaction step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations. Results-In PIVUS, 16 proteins were related to incident ischemic stroke using a false discovery rate of 5%. Of these, N-terminal pro-B-type natriuretic peptide (P=0.0032), adrenomedullin (P=0.018), and eosinophil cationic protein (P=0.0071) were replicated in ULSAM after adjustment for established stroke risk factors. In predefined secondary meta-analyses of individual data, interleukin-27 subunit , growth/differentiation factor 15, urokinase plasminogen activator surface receptor, tumor necrosis factor receptor superfamily member 6, macrophage colony-stimulating factor 1, and matrix metalloproteinase-7 were also potential risk markers for ischemic stroke after adjustment for multiple comparisons (P<0.0006). The addition of N-terminal pro-B-type natriuretic peptide, adrenomedullin, and eosinophil cationic protein to a model with established risk factors increased the C-statistic from 0.629 to 0.689 (P=0.001). Conclusions-Our data suggest that large-scale proteomics analysis is a promising way of discovering novel biomarkers that could substantially improve the prediction of ischemic stroke.

  • 154.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hedenstierna laboratory.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ärnlov, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Div Family Med, Dept Neurobiol Care Sci & Soc, Huddinge, 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, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Longitudinal effects of aging on plasma proteins levels in older adults - associations with kidney function and hemoglobin levels2019In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 2, article id e0212060Article in journal (Refereed)
    Abstract [en]

    Background A targeted proteomics chip has been shown to be useful to discover novel associations of proteins with cardiovascular disease. We investigated how these proteins change with aging, and whether this change is related to a decline in kidney function, or to a change in hemoglobin levels. Material and methods In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, including 1,016 participants from the general population aged 70 at baseline, 84 proteins were measured at ages 70, 75, 80. At these occasions, glomerular filtration rate (eGFR) was estimated and the hemoglobin levels were measured. Results Sixty-one of the 84 evaluated proteins changed significantly during the 10-year follow-up (multiple testing-adjusted alpha = 0.00059), most showing an increase. The change in eGFR was inversely related to changes of protein levels for the vast majority of proteins (74%). The change in hemoglobin was significantly related to the change in 40% of the evaluated proteins, with no obvious preference of the direction of these relationships. Conclusion The majority of evaluated proteins increased with aging in adults. Therefore, normal ranges for proteins might be given in age-strata. The increase in protein levels was associated with the degree of reduction in eGFR for the majority of proteins, while no clear pattern was seen for the relationships between the proteins and the change in hemoglobin levels. Studies on changes in urinary proteins are warranted to understand the association between the reduction in eGFR and increase in plasma protein levels.

  • 155.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    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.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalarna Univ, Dept Hlth & Social Sci, Falun, Sweden..
    Discovery of new biomarkers for atrial fibrillation using a custom-made proteomics chip2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 5, p. 379-384Article in journal (Refereed)
    Abstract [en]

    Background Apart from several established clinical risk factors for atrial fibrillation (AF), a number of biomarkers have also been identified as potential risk factors for AF. None of these have so far been adopted in clinical practice. Objective To use a novel custom-made proteomics chip to discover new prognostic biomarkers for AF risk. Methods In two independent community-based cohorts (Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (978 participants without AF, mean age 70.1 years, 50% women, median followup 10.0 years) and Uppsala Longitudinal Study of Adult Men (ULSAM) (n= 725, mean age 77.5 years, median follow-up 7.9 years)), ninety-two plasma proteins were assessed at baseline by a proximity extension assay (PEA) chip. Of those, 85 proteins showed a call rate > 70% in both cohorts. Results Thirteen proteins were related to incident AF in PIVUS (148 events) using a false discovery rate of 5%. Of those, five were replicated in ULSAM at nominal multivariable p value (123 events, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), fibroblast growth factor 23 (FGF-23), fatty acid-binding protein 4 (FABP4), growth differentiation factor 15 (GDF-15) and interleukin-6 (IL-6)). Of those, NT-pro-BNP and FGF-23 were also associated with AF after adjusting for established AF risk factors. In a prespecified secondary analysis pooling the two data sets, T-cell immunoglobulin and mucin domain 1 (TIM-1) and adrenomedullin (AM) were also significantly related to incident AF in addition to the aforementioned five proteins (Bonferroni-adjustment). The addition of NT-proBNP to a model with established risk factors increased the C-statistic from 0.605 to 0.676 (p< 0.0001). Conclusions Using a novel proteomics approach, we confirmed the previously reported association between NT-pro-BNP, FGF-23, GDF-15 and incident AF, and also discovered four proteins (FABP4, IL-6, TIM-1 and AM) that could be of importance in the development of AF.

  • 156.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med, Stockholm, Sweden.
    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, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA.
    Proteomic profiling of endothelium-dependent vasodilation2019In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 37, no 1, p. 216-222Article in journal (Refereed)
    Abstract [en]

    Objective: As endothelial dysfunction is an early event in atherosclerosis formation, we investigated if proteins previously related to cardiovascular disease also were related to endothelial function using a novel targeted proteomics approach.

    Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 850970, all aged 70 years), endothelium-dependent vasodilation (EDV) in the forearm was assessed by intraarterial infusion of acetylcholine. Flow-mediated vasodilation (FMD) was investigated in the brachial artery by ultrasound. The same investigations were carried out in the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n = 375-461, all aged 50 years). After strict quality control, 84 cardiovascular-related proteins measured by the proximity extension assay were studied in relation to EDV and FMD in PIVUS (discovery sample) and POEM (validation sample).

    Results: Of the 15 proteins being significantly related to EDV in PIVUS (false discovery rate < 0.025), seven could be replicated in POEM at nominal significance and same effect direction when adjusted for sex and storage time. Of those, only cathepsin D remained significant following further adjustment for traditional cardiovascular risk factors (beta, -0.08; 95% confidence interval, -0.16, -0.01; P = 0.033; change in ln-transformed EDV per 1-SD increase in protein level). No protein was significantly related to FMD.

    Conclusion: Using a discovery/validation approach in two samples, our results indicate an inverse association between plasma cathepsin D levels and endothelial-dependent vasodilation.

  • 157.
    Lind, Lars
    et al.
    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.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Siegbahn, Agneta
    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.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    Use of a proximity extension assay proteomics chip to discover new biomarkers for human atherosclerosis2015In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 242, no 1, p. 205-210Article in journal (Refereed)
    Abstract [en]

    Background and aims: We used a proteomics array to simultaneously measure multiple proteins that have been suggested to be associated with atherosclerosis and related them to plaque prevalence in carotid arteries in a human population-based study. Methods: In the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS; n = 931, 50% women, all aged 70 years), the number of carotid arteries with plaques was recorded by ultrasound. Levels of 82 proteins were assessed in plasma by a proximity extension assay (Proseek Multiplex CVD, Olink Bioscience, Uppsala, Sweden) and related to carotid measures in a regression framework. Results: Following adjustment for multiple testing with Bonferroni correction, seven of the proteins were significantly related to the number of carotid arteries affected by plaques in sex-adjusted models (osteoprotegrin, T-cell immunoglobulin and mucin domain (TIM)-1, growth/differentiation factor 15 (GDF-15), matrix metalloprotease-12 (MMP-12), renin, tumor necrosis factor ligand superfamily member 14 (TNFSF14) and growth hormone). Of these, renin (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.13-1.49 per standard deviation increase), growth hormone (OR, 1.24; 95% CI, 1.08-1.43), osteoprotegerin (OR, 1.22; 95% CI, 1.05-1.43) and TNFSF14 (OR, 1.17; 95% CI, 1.01-1.35) were related to plaque prevalence independently of each other and traditional cardiovascular risk factors. Conclusion: A novel targeted proteomics approach using the proximity extension technique discovered several new associations of candidate proteins with carotid artery plaque prevalence in a large human sample.

  • 158.
    Lind, Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Univ Orebro, MTM Res Ctr, Sch Sci & Technol, SE-70182 Orebro, Sweden..
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    van Bavel, B.
    Univ Orebro, MTM Res Ctr, Sch Sci & Technol, SE-70182 Orebro, Sweden..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Circulating levels of perfluoroalkyl substances and biomarkers of liver function in a large population based sample of elderly men and women from Sweden2015In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 238, no 2, p. S91-S91Article in journal (Other academic)
  • 159.
    Lind, Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    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. Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Stubleski, Jordan
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Kärrman, Anna
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Van Bavel, Bert
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    The changes in plasma levels of perfluoroalkyl substances (PFASs) are related to the increase in carotid intima-media thickness over 10 years2017In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 263, p. E18-E18Article in journal (Other academic)
  • 160.
    Lind, P. Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    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. MTM Research Center, School of Science and Technology, Örebro University, Örebro, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    High plasma organochlorine pesticide levels are related to increased biological age as calculated by DNA methylation analysis2018In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 113, p. 109-113Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Organochlorine pesticides (OCPs) have been shown in the experimental setting to alter DNA methylation. Since DNA methylation changes during the life-span, formulas have been presented to calculate "DNA methylation age" as a measure of biological age.

    OBJECTIVES: We aimed to investigate if circulating levels of three OCPs were related to increased DNA methylation age METHODS: 71CpG DNA methylation age (Hannum formula) was calculated based on data from the Illumina 450 k Bead Methylation chip in 1000 subjects in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years at the examination). The difference between DNA methylation age and chronological age was calculated (DiffAge). 2,2-bis (4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE), hexachlorobenzene (HCB), and transnonachlor (TNC) levels were measured in plasma by high-resolution gas chromatography coupled mass spectrometry (HRGC-HRMS).

    RESULTS: Increased p,p'-DDE and TNC, but not HCB, levels were related to increased DiffAge both in sex and BMI-adjusted models, as well as in multiple adjusted models (sex, education level, exercise habits, smoking, energy and alcohol consumption and BMI) (p = 0.0051 and p = 0.011, respectively). No significant interactions between the OCPs and sex or BMI regarding DiffAge were found.

    CONCLUSION: In this cross-sectional study, increased levels of two out of three OCPs were related to increased DNA methylation age, further suggesting negative health effects in humans of these widespread environmental contaminants.

  • 161.
    Lind, P. Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    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. Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Stubleski, Jordan
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Kärrman, Anna
    Orebro Univ, Sch Sci & Technol, MTM Res Ctr, Orebro, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Changes in plasma levels of perfluoroalkyl substances (PFASs) are related to increase in carotid intima-media thickness over 10 years - a longitudinal study2018In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 17, article id 59Article in journal (Refereed)
    Abstract [en]

    Background: It has previously been reported that the environmental contaminants perfluoroalkyl substances (PFASs) are linked to atherosclerosis in cross-sectional studies. Since cross-sectional studies could be subject to reverse causation, the purpose of this study was to analyze if the longitudinal changes in PFASs during a 10-year follow-up were related to the change in carotid artery intima-media thickness (IMT, ultrasound) during the same period.

    Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, 1016 individuals were investigated at age 70; 826 of them were reinvestigated at age 75 and 602 at age 80 years. Eight different PFASs were measured in plasma by ultra-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and IMT was measured at all three time points. Random-effects mixed regression models were used to examine the associations over time.

    Results: IMT increased 0.058 mm during the 10-year period (p <0.0001). Following adjustment for baseline values of PFASs (age 70) and sex, the changes in plasma levels of 6 of the 8 measured PFASs were significantly related to the change in IMT over the 10-year follow-up period in a positive fashion (p <0.0062 using Bonferroni correction for 8 tests). Further adjustment for traditional cardiovascular (CV) risk factors (HDL and LDL cholesterol, smoking, systolic blood pressure, statin use, fasting glucose and serum triglycerides) affected these relationships only marginally.

    Conclusion: The change in plasma levels of several PFASs during 10 years was positively related to increase in IMT seen during the same period, giving prospective evidence that PFASs might interfere with the atherosclerotic process.

  • 162.
    Lind, P. Monica
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    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. MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden.
    van Bavel, Bert
    MTM Research Centre, School of Science and Technology, Örebro University, Örebro, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Circulating levels of perfluoroalkyl substances (PFASs) and carotid artery atherosclerosis2017In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 152, p. 157-164Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVE: During recent years, some persistent organic pollutants (POPs) have been linked to atherosclerosis. One group of POPs, the poly- and perfluoroalkyl substances (PFASs) have not been investigated with regard to atherosclerotic plaques.

    METHODS: Carotid artery atherosclerosis was assessed by ultrasound in 1016 subjects aged 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eight PFASs were detected in >75% of participants' plasma by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).

    RESULTS: No significant linear associations were observed between the PFASs and intima-media thickness (IMT), or the echogenicity in the intima-media complex (IM-GSM, a marker of lipid infiltration in the artery) when men and women were analyzed together. Neither was occurrence of carotid plaques related to PFASs levels. However, highly significant interactions were observed between some PFASs and sex regarding both IM-GSM and plaque prevalence. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), were all related to IM-GSM in a positive fashion in women (p=0.002-0.003), while these relationships were negative in men. The levels of PFUnDA were significantly related to carotid plaque in women (OR 1.59, 95%CI 1.03-2.43, p=0.03), but not in men (OR 0.93, 95%CI 0.62-1.42, p=0.75).

    CONCLUSIONS: In this cross-sectional study, a pronounced gender difference was observed regarding associations between some PFASs, especially the long-chain PFUnDA, and markers of atherosclerosis, with more pronounced relationships found in women. These findings suggest a sex-specific role for PFASs in atherosclerosis.

  • 163. Lindgren, Emma
    et al.
    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.
    Giordano, Fosco
    Börkegren, Johan
    Ström, Lena
    Inactivation of the budding yeast cohesin loader Scc2 alters gene expression both globally and in response to a single DNA double strand break2014In: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 13, no 23, p. 3645-3658Article in journal (Refereed)
    Abstract [en]

    Genome integrity is fundamental for cell survival and cell cycle progression. Important mechanisms for keeping the genome intact are proper sister chromatid segregation, correct gene regulation and efficient repair of damaged DNA. Cohesin and its DNA loader, the Scc2/4 complex have been implicated in all these cellular actions. The gene regulation role has been described in several organisms. In yeast it has been suggested that the proteins in the cohesin network would effect transcription based on its role as insulator. More recently, data are emerging indicating direct roles for gene regulation also in yeast. Here we extend these studies by investigating whether the cohesin loader Scc2 is involved in regulation of gene expression. We performed global gene expression profiling in the absence and presence of DNA damage, in wild type and Scc2 deficient G2/M arrested cells, when it is known that Scc2 is important for DNA double strand break repair and formation of damage induced cohesion. We found that not only the DNA damage specific transcriptional response is distorted after inactivation of Scc2 but also the overall transcription profile. Interestingly, these alterations did not correlate with changes in cohesin binding.

  • 164. Liu, C
    et al.
    Marioni, R E
    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.
    Pfeiffer, L
    Tsai, P-C
    Reynolds, L M
    Just, A C
    Duan, Q
    Boer, C G
    Tanaka, T
    Elks, C E
    Aslibekyan, S
    Brody, J A
    Kühnel, B
    Herder, C
    Almli, L M
    Zhi, D
    Wang, Y
    Huan, T
    Yao, C
    Mendelson, M M
    Joehanes, R
    Liang, L
    Love, S-A
    Guan, W
    Shah, S
    McRae, A F
    Kretschmer, A
    Prokisch, H
    Strauch, K
    Peters, A
    Visscher, P M
    Wray, N R
    Guo, X
    Wiggins, K L
    Smith, A K
    Binder, E B
    Ressler, K J
    Irvin, M R
    Absher, D M
    Hernandez, D
    Ferrucci, L
    Bandinelli, S
    Lohman, K
    Ding, J
    Trevisi, 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.
    Sandling, Johanna K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Rheumatology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Stolk, L
    Uitterlinden, A G
    Yet, I
    Castillo-Fernandez, J E
    Spector, T D
    Schwartz, J D
    Vokonas, P
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Li, Y
    Fornage, M
    Arnett, D K
    Wareham, N J
    Sotoodehnia, N
    Ong, K K
    van Meurs, J B J
    Conneely, K N
    Baccarelli, A A
    Deary, I J
    Bell, J T
    North, K E
    Liu, Y
    Waldenberger, M
    London, S J
    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. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
    Levy, D
    A DNA methylation biomarker of alcohol consumption.2018In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 23, p. 422-433Article in journal (Refereed)
    Abstract [en]

    The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10(-7). Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10(-7). In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.

  • 165.
    Ljungberg, Johan
    et al.
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden..
    Janiec, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Bergdahl, Ingvar A.
    Umea Univ, Dept Biobank Res, Umea, Sweden..
    Holmgren, Anders
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden..
    Hultdin, Johan
    Umea Univ, Dept Med Biosci, Umea, Sweden..
    Johansson, Bengt
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden..
    Näslund, Ulf
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical 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.
    Söderberg, Stefan
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden..
    Proteomic Biomarkers for Incident Aortic Stenosis Requiring Valvular Replacement2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 138, no 6, p. 590-599Article in journal (Refereed)
    Abstract [en]

    Background: Aortic valve stenosis (AS) is the most common indication for cardiac valve surgery; untreated AS is linked to high mortality. The etiological background of AS is unknown. Previous human studies were typically based on case-control studies. Biomarkers identified in prospective studies could lead to novel mechanistic insights.

    Methods: Within a large population survey with blood samples obtained at baseline, 334 patients were identified who later underwent surgery for AS (median age [interquartile range], 59.9 [10.4] years at survey and 68.3 [12.7] at surgery; 48% female). For each case, 2 matched referents were allocated. Plasma was analyzed with the multiplex proximity extension assay for screening of 92 cardiovascular candidate proteins. Conditional logistic regression models were used to assess associations between each protein and AS, with correction for multiple testing. A separate set of 106 additional cases with 212 matched referents was used in a validation study.

    Results: Six proteins (growth differentiation factor 15, galectin-4, von Willebrand factor, interleukin 17 receptor A, transferrin receptor protein 1, and proprotein convertase subtilisin/kexin type 9) were associated with case status in the discovery cohort; odds ratios ranged from 1.25 to 1.37 per SD increase in the protein signal. Adjusting the multivariable models for classical cardiovascular risk factors at baseline yielded similar results. Subanalyses of case-referent triplets (n=133) who showed no visible coronary artery disease at the time of surgery in the index person supported associations between AS and growth differentiation factor 15 (odds ratio, 1.40; 95% confidence interval, 1.10-1.78) and galectin-4 (odds ratio, 1.27; 95% confidence interval, 1.02-1.59), but these associations were attenuated after excluding individuals who donated blood samples within 5 years before surgery. In triplets (n=201), which included index individuals with concurrent coronary artery disease at the time of surgery, all 6 proteins were robustly associated with case status in all sensitivity analyses. In the validation study, the association of all but 1 (interleukin 17 receptor A) of these proteins were replicated in patients with AS with concurrent coronary artery disease but not in patients with AS without coronary artery disease.

    Conclusions: We provide evidence that 5 proteins were altered years before AS surgery and that the associations seem to be driven by concurrent atherosclerotic disease.

  • 166. Locke, Adam E
    et al.
    Kahali, Bratati
    Berndt, Sonja I
    Justice, Anne E
    Pers, Tune H
    Day, Felix R
    Powell, Corey
    Vedantam, Sailaja
    Buchkovich, Martin L
    Yang, Jian
    Croteau-Chonka, Damien C
    Esko, Tonu
    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.
    Ferreira, Teresa
    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.
    Kutalik, Zoltán
    Luan, Jian'an
    Mägi, Reedik
    Randall, Joshua C
    Winkler, Thomas W
    Wood, Andrew R
    Workalemahu, Tsegaselassie
    Faul, Jessica D
    Smith, Jennifer A
    Hua Zhao, Jing
    Zhao, Wei
    Chen, Jin
    Fehrmann, Rudolf
    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.
    Karjalainen, Juha
    Schmidt, Ellen M
    Absher, Devin
    Amin, Najaf
    Anderson, Denise
    Beekman, Marian
    Bolton, Jennifer L
    Bragg-Gresham, Jennifer L
    Buyske, Steven
    Demirkan, Ayse
    Deng, Guohong
    Ehret, Georg B
    Feenstra, Bjarke
    Feitosa, Mary F
    Fischer, Krista
    Goel, Anuj
    Gong, Jian
    Jackson, Anne U
    Kanoni, Stavroula
    Kleber, Marcus E
    Kristiansson, Kati
    Lim, Unhee
    Lotay, Vaneet
    Mangino, Massimo
    Mateo Leach, Irene
    Medina-Gomez, Carolina
    Medland, Sarah E
    Nalls, Michael A
    Palmer, Cameron D
    Pasko, Dorota
    Pechlivanis, Sonali
    Peters, Marjolein J
    Prokopenko, Inga
    Shungin, Dmitry
    Stančáková, Alena
    Strawbridge, Rona J
    Ju Sung, Yun
    Tanaka, Toshiko
    Teumer, Alexander
    Trompet, Stella
    van der Laan, Sander W
    van Setten, Jessica
    Van Vliet-Ostaptchouk, Jana V
    Wang, Zhaoming
    Yengo, Loïc
    Zhang, Weihua
    Isaacs, Aaron
    Albrecht, Eva
    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.
    Arscott, Gillian M
    Attwood, Antony P
    Bandinelli, Stefania
    Barrett, Amy
    Bas, Isabelita N
    Bellis, Claire
    Bennett, Amanda J
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Blagieva, Roza
    Blüher, Matthias
    Böhringer, Stefan
    Bonnycastle, Lori L
    Böttcher, Yvonne
    Boyd, Heather A
    Bruinenberg, Marcel
    Caspersen, Ida H
    Ida Chen, Yii-Der
    Clarke, Robert
    Warwick Daw, E
    de Craen, Anton J M
    Delgado, Graciela
    Dimitriou, Maria
    Doney, Alex S F
    Eklund, Niina
    Estrada, Karol
    Eury, Elodie
    Folkersen, Lasse
    Fraser, Ross M
    Garcia, Melissa E
    Geller, Frank
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gigante, Bruna
    Go, Alan S
    Golay, Alain
    Goodall, Alison H
    Gordon, Scott D
    Gorski, Mathias
    Grabe, Hans-Jörgen
    Grallert, Harald
    Grammer, Tanja B
    Gräßler, Jürgen
    Grönberg, Henrik
    Groves, Christopher J
    Gusto, Gaëlle
    Haessler, Jeffrey
    Hall, Per
    Haller, Toomas
    Hallmans, Goran
    Hartman, Catharina A
    Hassinen, Maija
    Hayward, Caroline
    Heard-Costa, Nancy L
    Helmer, Quinta
    Hengstenberg, Christian
    Holmen, Oddgeir
    Hottenga, Jouke-Jan
    James, Alan L
    Jeff, Janina M
    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.
    Jolley, Jennifer
    Juliusdottir, Thorhildur
    Kinnunen, Leena
    Koenig, Wolfgang
    Koskenvuo, Markku
    Kratzer, Wolfgang
    Laitinen, Jaana
    Lamina, Claudia
    Leander, Karin
    Lee, Nanette R
    Lichtner, Peter
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindström, Jaana
    Sin Lo, Ken
    Lobbens, Stéphane
    Lorbeer, Roberto
    Lu, Yingchang
    Mach, François
    Magnusson, Patrik K E
    Mahajan, Anubha
    McArdle, Wendy L
    McLachlan, Stela
    Menni, Cristina
    Merger, Sigrun
    Mihailov, Evelin
    Milani, Lili
    Moayyeri, Alireza
    Monda, Keri L
    Morken, Mario A
    Mulas, Antonella
    Müller, Gabriele
    Müller-Nurasyid, Martina
    Musk, Arthur W
    Nagaraja, Ramaiah
    Nöthen, Markus M
    Nolte, Ilja M
    Pilz, Stefan
    Rayner, Nigel W
    Renstrom, Frida
    Rettig, Rainer
    Ried, Janina S
    Ripke, Stephan
    Robertson, Neil R
    Rose, Lynda M
    Sanna, Serena
    Scharnagl, Hubert
    Scholtens, Salome
    Schumacher, Fredrick R
    Scott, William R
    Seufferlein, Thomas
    Shi, Jianxin
    Vernon Smith, Albert
    Smolonska, Joanna
    Stanton, Alice V
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen
    Stringham, Heather M
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Swertz, Morris A
    Swift, Amy J
    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.
    Tan, Sian-Tsung
    Tayo, Bamidele O
    Thorand, Barbara
    Thorleifsson, Gudmar
    Tyrer, Jonathan P
    Uh, Hae-Won
    Vandenput, Liesbeth
    Verhulst, Frank C
    Vermeulen, Sita H
    Verweij, Niek
    Vonk, Judith M
    Waite, Lindsay L
    Warren, Helen R
    Waterworth, Dawn
    Weedon, Michael N
    Wilkens, Lynne R
    Willenborg, Christina
    Wilsgaard, Tom
    Wojczynski, Mary K
    Wong, Andrew
    Wright, Alan F
    Zhang, Qunyuan
    Brennan, Eoin P
    Choi, Murim
    Dastani, Zari
    Drong, Alexander W
    Eriksson, Per
    Franco-Cereceda, Anders
    Gådin, Jesper R
    Gharavi, Ali G
    Goddard, Michael E
    Handsaker, Robert E
    Huang, Jinyan
    Karpe, Fredrik
    Kathiresan, Sekar
    Keildson, Sarah
    Kiryluk, Krzysztof
    Kubo, Michiaki
    Lee, Jong-Young
    Liang, Liming
    Lifton, Richard P
    Ma, Baoshan
    McCarroll, Steven A
    McKnight, Amy J
    Min, Josine L
    Moffatt, Miriam F
    Montgomery, Grant W
    Murabito, Joanne M
    Nicholson, George
    Nyholt, Dale R
    Okada, Yukinori
    Perry, John R B
    Dorajoo, Rajkumar
    Reinmaa, Eva
    Salem, Rany M
    Sandholm, Niina
    Scott, Robert A
    Stolk, Lisette
    Takahashi, Atsushi
    Tanaka, Toshihiro
    Van't Hooft, Ferdinand M
    Vinkhuyzen, Anna A E
    Westra, Harm-Jan
    Zheng, Wei
    Zondervan, Krina T
    Heath, Andrew C
    Arveiler, Dominique
    Bakker, Stephan J L
    Beilby, John
    Bergman, Richard N
    Blangero, John
    Bovet, Pascal
    Campbell, Harry
    Caulfield, Mark J
    Cesana, Giancarlo
    Chakravarti, Aravinda
    Chasman, Daniel I
    Chines, Peter S
    Collins, Francis S
    Crawford, Dana C
    Adrienne Cupples, L
    Cusi, Daniele
    Danesh, John
    de Faire, Ulf
    den Ruijter, Hester M
    Dominiczak, Anna F
    Erbel, Raimund
    Erdmann, Jeanette
    Eriksson, Johan G
    Farrall, Martin
    Felix, Stephan B
    Ferrannini, Ele
    Ferrières, Jean
    Ford, Ian
    Forouhi, Nita G
    Forrester, Terrence
    Franco, Oscar H
    Gansevoort, Ron T
    Gejman, Pablo V
    Gieger, Christian
    Gottesman, Omri
    Gudnason, Vilmundur
    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.
    Hall, Alistair S
    Harris, Tamara B
    Hattersley, Andrew T
    Hicks, Andrew A
    Hindorff, Lucia A
    Hingorani, Aroon D
    Hofman, Albert
    Homuth, Georg
    Kees Hovingh, G
    Humphries, Steve E
    Hunt, Steven C
    Hyppönen, Elina
    Illig, Thomas
    Jacobs, Kevin B
    Jarvelin, Marjo-Riitta
    Jöckel, Karl-Heinz
    Johansen, Berit
    Jousilahti, Pekka
    Wouter Jukema, J
    Jula, Antti M
    Kaprio, Jaakko
    Kastelein, John J P
    Keinanen-Kiukaanniemi, Sirkka M
    Kiemeney, Lambertus A
    Knekt, Paul
    Kooner, Jaspal S
    Kooperberg, Charles
    Kovacs, Peter
    Kraja, Aldi T
    Kumari, Meena
    Kuusisto, Johanna
    Lakka, Timo A
    Langenberg, Claudia
    Le Marchand, Loic
    Lehtimäki, Terho
    Lyssenko, Valeriya
    Männistö, Satu
    Marette, André
    Matise, Tara C
    McKenzie, Colin A
    McKnight, Barbara
    Moll, Frans L
    Morris, Andrew D
    Morris, Andrew P
    Murray, Jeffrey C
    Nelis, Mari
    Ohlsson, Claes
    Oldehinkel, Albertine J
    Ong, Ken K
    Madden, Pamela A F
    Pasterkamp, Gerard
    Peden, John F
    Peters, Annette
    Postma, Dirkje S
    Pramstaller, Peter P
    Price, Jackie F
    Qi, Lu
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Ridker, Paul M
    Rioux, John D
    Ritchie, Marylyn D
    Rudan, Igor
    Salomaa, Veikko
    Samani, Nilesh J
    Saramies, Jouko
    Sarzynski, Mark A
    Schunkert, Heribert
    Schwarz, Peter E H
    Sever, Peter
    Shuldiner, Alan R
    Sinisalo, Juha
    Stolk, Ronald P
    Strauch, Konstantin
    Tönjes, Anke
    Trégouët, David-Alexandre
    Tremblay, Angelo
    Tremoli, Elena
    Virtamo, Jarmo
    Vohl, Marie-Claude
    Völker, Uwe
    Waeber, Gérard
    Willemsen, Gonneke
    Witteman, Jacqueline C
    Zillikens, M Carola
    Adair, Linda S
    Amouyel, Philippe
    Asselbergs, Folkert W
    Assimes, Themistocles L
    Bochud, Murielle
    Boehm, Bernhard O
    Boerwinkle, Eric
    Bornstein, Stefan R
    Bottinger, Erwin P
    Bouchard, Claude
    Cauchi, Stéphane
    Chambers, John C
    Chanock, Stephen J
    Cooper, Richard S
    de Bakker, Paul I W
    Dedoussis, George
    Ferrucci, Luigi
    Franks, Paul W
    Froguel, Philippe
    Groop, Leif C
    Haiman, Christopher A
    Hamsten, Anders
    Hui, Jennie
    Hunter, David J
    Hveem, Kristian
    Kaplan, Robert C
    Kivimaki, Mika
    Kuh, Diana
    Laakso, Markku
    Liu, Yongmei
    Martin, Nicholas G
    März, Winfried
    Melbye, Mads
    Metspalu, Andres
    Moebus, Susanne
    Munroe, Patricia B
    Njølstad, Inger
    Oostra, Ben A
    Palmer, Colin N A
    Pedersen, Nancy L
    Perola, Markus
    Pérusse, Louis
    Peters, Ulrike
    Power, Chris
    Quertermous, Thomas
    Rauramaa, Rainer
    Rivadeneira, Fernando
    Saaristo, Timo E
    Saleheen, Danish
    Sattar, Naveed
    Schadt, Eric E
    Schlessinger, David
    Eline Slagboom, P
    Snieder, Harold
    Spector, Tim D
    Thorsteinsdottir, Unnur
    Stumvoll, Michael
    Tuomilehto, Jaakko
    Uitterlinden, André G
    Uusitupa, Matti
    van der Harst, Pim
    Walker, Mark
    Wallaschofski, Henri
    Wareham, Nicholas J
    Watkins, Hugh
    Weir, David R
    Wichmann, H-Erich
    Wilson, James F
    Zanen, Pieter
    Borecki, Ingrid B
    Deloukas, Panos
    Fox, Caroline S
    Heid, Iris M
    O'Connell, Jeffrey R
    Strachan, David P
    Stefansson, Kari
    van Duijn, Cornelia M
    Abecasis, Gonçalo R
    Franke, Lude
    Frayling, Timothy M
    McCarthy, Mark I
    Visscher, Peter M
    Scherag, André
    Willer, Cristen J
    Boehnke, Michael
    Mohlke, Karen L
    Lindgren, Cecilia M
    Beckmann, Jacques S
    Barroso, Inês
    North, Kari E
    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.
    Hirschhorn, Joel N
    Loos, Ruth J F
    Speliotes, Elizabeth K
    Genetic studies of body mass index yield new insights for obesity biology2015In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 518, no 7538, p. 197-206Article in journal (Refereed)
    Abstract [en]

    Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10−8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ~2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

  • 167.
    Loley, Christina
    et al.
    Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometrie & Stat, Campus Lubeck, Lubeck, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Hamburg Lubeck Kiel, Lubeck, Germany..
    Alver, Maris
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Inst Mol & Cell Biol, Tartu, Estonia..
    Assimes, Themistocles L.
    Stanford Univ, Sch Med Stanford, Dept Med, Div Cardiovasc Med, Stanford, CA USA..
    Bjonnes, Andrew
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA..
    Goel, Anuj
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    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.
    Hernesniemi, Jussi
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Heart Hosp, Dept Cariol, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, CTSU, Oxford, England..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Kleber, Marcus E.
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany..
    Lau, King Wai
    Univ Oxford, Nuffield Dept Populat Hlth, CTSU, Oxford, England..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere, Finland..
    Nelson, Christopher P.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Nikpay, Majid
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Qu, Liming
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Salfati, Elias
    Stanford Univ, Sch Med Stanford, Dept Med, Div Cardiovasc Med, Stanford, CA USA..
    Scholz, Markus
    Univ Leipzig, Fac Med, Inst Med Informat Stat & Epidemiol, Leipzig, Germany.;LIFE Res Ctr Civilizat Dis, Leipzig, Germany..
    Tukiainen, Taru
    Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA..
    Willenborg, Christina
    DZHK German Ctr Cardiovasc Res, Partner Site Hamburg Lubeck Kiel, Lubeck, Germany.;Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Integrat & Expt Genom, Campus Lubeck, Lubeck, Germany.;Univ Heart Ctr Luebeck, Campus Lubeck, Lubeck, Germany..
    Won, Hong-Hee
    Sungkyunkwan Univ, Samsung Med Ctr, SAIHST, Seoul, South Korea..
    Zeng, Lingyao
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Zhang, Weihua
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.;Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England..
    Anand, Sonia S.
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Beutner, Frank
    LIFE Res Ctr Civilizat Dis, Leipzig, Germany.;Univ Leipzig, Heart Ctr Leipzig, Cardiol, Leipzig, Germany..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Clarke, Robert
    Univ Oxford, Nuffield Dept Populat Hlth, CTSU, Oxford, England..
    Dedoussis, George
    Harokopio Univ Athens, Athens, Greece..
    Do, Ron
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Ctr Stat Genet, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Zena & Michael A Weiner Cardiovasc Inst, New York, NY 10029 USA..
    Esko, Tonu
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Harvard Med Sch, Dept Med, Boston, MA USA..
    Eskola, Markku
    Heart Hosp, Dept Cariol, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Farrall, Martin
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Gauguier, Dominique
    INSERM, Ctr Rech Cordeliers, UMRS1138, Paris, France..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Granger, Christopher B.
    Duke Univ, Sch Med, Durham, NC USA..
    Hall, Alistair S.
    Univ Leeds, Leeds Inst Genet Hlth & Therapeut, Leeds LS2 9JT, W Yorkshire, England..
    Hamsten, Anders
    Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Cardiovasc Genet & Genom Grp, Stockholm, Sweden..
    Hazen, Stanley L.
    Cleveland Clin, Cleveland, OH 44106 USA..
    Huang, Jie
    Boston VA Res Inst Inc, Boston, MA USA..
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Physiol, Tampere, Finland..
    Kyriakou, Theodosios
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Laaksonen, Reijo
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere, Finland.;Zora Biosci, Espoo, Finland..
    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.;MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA.;Harvard Univ, Cambridge, MA 02138 USA..
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Marouli, Eirini
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England..
    Nikus, Kjell
    Heart Hosp, Dept Cariol, Tampere, Finland.;Univ Tampere, Sch Med, Tampere, Finland..
    Pedersen, Nancy
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Rallidis, Loukianos
    Univ Gen Hosp Attikon, Dept Cardiol 2, Athens, Greece..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland..
    Shah, Svati H.
    Duke Univ, Sch Med, Durham, NC USA..
    Stewart, Alexandre F. R.
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Thompson, John R.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Zalloua, Pierre A.
    Lebanese Amer Univ, Sch Med, Beirut, Lebanon.;Harvard Sch Publ Hlth, Boston, MA USA..
    Chambers, John C.
    Ealing Hosp Natl Hlth Serv NHS Trust, Dept Cardiol, Southall, Middx, England.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.;Imperial Coll Healthcare NHS Trust, London, England..
    Collins, Rory
    Univ Oxford, Nuffield Dept Populat Hlth, CTSU, Oxford, 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. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Iribarren, Carlos
    Kaiser Permanente, Div Res, Oakland, CA USA..
    Karhunen, Pekka J.
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Forens Med, Tampere, Finland..
    Kooner, Jaspal S.
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.;Imperial Coll Healthcare NHS Trust, London, England.;Imperial Coll London, Cardiovasc Sci, Natl Heart & Lung Inst, London, England..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere, Finland..
    Loos, Ruth J. F.
    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..
    Maerz, Winfried
    Heidelberg Univ, Med Fac Mannheim, Dept Med 5, Mannheim, Germany.;Synlab Serv GmbH, Synlab Acad, Mannheim, Germany.;Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria..
    McPherson, Ruth
    Univ Ottawa, Inst Heart, Ruddy Canadian Cardiovasc Genet Ctr, Ottawa, ON, Canada..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.;Inst Mol & Cell Biol, Tartu, Estonia..
    Reilly, Muredach P.
    Univ Penn, Cardiovasc Inst, Perelman Sch Med, Philadelphia, PA 19104 USA..
    Ripatti, Samuli
    Kaiser Permanente, Div Res, Oakland, CA USA.;Univ Helsinki, Hjelt Inst, Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland..
    Sanghera, Dharambir K.
    Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73190 USA.;Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73190 USA.;Oklahoma Ctr Neurosci, Oklahoma City, OK USA..
    Thiery, Joachim
    LIFE Res Ctr Civilizat Dis, Leipzig, Germany.;Univ Hosp Leipzig, Fac Med, Inst Lab Med Clin Chem & Mol Diagnost, Leipzig, Germany..
    Watkins, Hugh
    Univ Oxford, Div Cardiovasc Med, Radcliffe Dept Med, Oxford, England.;Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England..
    Deloukas, Panos
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.;Wellcome Trust Sanger Inst, Cambridge, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah, Saudi Arabia..
    Kathiresan, Sekar
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Med, Boston, MA USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA..
    Samani, Nilesh J.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    Schunkert, Heribert
    DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany.;Imperial Coll London, Dept Epidemiol & Biostat, London, England..
    Erdmann, Jeanette
    DZHK German Ctr Cardiovasc Res, Partner Site Hamburg Lubeck Kiel, Lubeck, Germany.;Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Integrat & Expt Genom, Campus Lubeck, Lubeck, Germany.;Univ Heart Ctr Luebeck, Campus Lubeck, Lubeck, Germany..
    Koenig, Inke R.
    Univ Lubeck, Univ Klinikum Schleswig Holstein, Inst Med Biometrie & Stat, Campus Lubeck, Lubeck, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Hamburg Lubeck Kiel, Lubeck, Germany..
    No Association of Coronary Artery Disease with X-Chromosomal Variants in Comprehensive International Meta-Analysis2016In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, article id 35278Article in journal (Refereed)
    Abstract [en]

    In recent years, genome-wide association studies have identified 58 independent risk loci for coronary artery disease (CAD) on the autosome. However, due to the sex-specific data structure of the X chromosome, it has been excluded from most of these analyses. While females have 2 copies of chromosome X, males have only one. Also, one of the female X chromosomes may be inactivated. Therefore, special test statistics and quality control procedures are required. Thus, little is known about the role of X-chromosomal variants in CAD. To fill this gap, we conducted a comprehensive X-chromosome-wide meta-analysis including more than 43,000 CAD cases and 58,000 controls from 35 international study cohorts. For quality control, sex-specific filters were used to adequately take the special structure of X-chromosomal data into account. For single study analyses, several logistic regression models were calculated allowing for inactivation of one female X-chromosome, adjusting for sex and investigating interactions between sex and genetic variants. Then, meta-analyses including all 35 studies were conducted using random effects models. None of the investigated models revealed genome-wide significant associations for any variant. Although we analyzed the largest-to-date sample, currently available methods were not able to detect any associations of X-chromosomal variants with CAD.

  • 168. Loth, Daan W
    et al.
    Artigas, María Soler
    Gharib, Sina A
    Wain, Louise V
    Franceschini, Nora
    Koch, Beate
    Pottinger, Tess D
    Smith, Albert Vernon
    Duan, Qing
    Oldmeadow, Chris
    Lee, Mi Kyeong
    Strachan, David P
    James, Alan L
    Huffman, Jennifer E
    Vitart, Veronique
    Ramasamy, Adaikalavan
    Wareham, Nicholas J
    Kaprio, Jaakko
    Wang, Xin-Qun
    Trochet, Holly
    Kähönen, Mika
    Flexeder, Claudia
    Albrecht, Eva
    Lopez, Lorna M
    de Jong, Kim
    Thyagarajan, Bharat
    Alves, Alexessander Couto
    Enroth, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Omenaas, Ernst
    Joshi, Peter K
    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.
    Viñuela, Ana
    Launer, Lenore J
    Loehr, Laura R
    Fornage, Myriam
    Li, Guo
    Wilk, Jemma B
    Tang, Wenbo
    Manichaikul, Ani
    Lahousse, Lies
    Harris, Tamara B
    North, Kari E
    Rudnicka, Alicja R
    Hui, Jennie
    Gu, Xiangjun
    Lumley, Thomas
    Wright, Alan F
    Hastie, Nicholas D
    Campbell, Susan
    Kumar, Rajesh
    Pin, Isabelle
    Scott, Robert A
    Pietiläinen, Kirsi H
    Surakka, Ida
    Liu, Yongmei
    Holliday, Elizabeth G
    Schulz, Holger
    Heinrich, Joachim
    Davies, Gail
    Vonk, Judith M
    Wojczynski, Mary
    Pouta, Anneli
    Johansson, Åsa
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wild, Sarah H
    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.
    Rivadeneira, Fernando
    Völzke, Henry
    Hysi, Pirro G
    Eiriksdottir, Gudny
    Morrison, Alanna C
    Rotter, Jerome I
    Gao, Wei
    Postma, Dirkje S
    White, Wendy B
    Rich, Stephen S
    Hofman, Albert
    Aspelund, Thor
    Couper, David
    Smith, Lewis J
    Psaty, Bruce M
    Lohman, Kurt
    Burchard, Esteban G
    Uitterlinden, André G
    Garcia, Melissa
    Joubert, Bonnie R
    McArdle, Wendy L
    Musk, A Bill
    Hansel, Nadia
    Heckbert, Susan R
    Zgaga, Lina
    van Meurs, Joyce B J
    Navarro, Pau
    Rudan, Igor
    Oh, Yeon-Mok
    Redline, Susan
    Jarvis, Deborah L
    Zhao, Jing Hua
    Rantanen, Taina
    O'Connor, George T
    Ripatti, Samuli
    Scott, Rodney J
    Karrasch, Stefan
    Grallert, Harald
    Gaddis, Nathan C
    Starr, John M
    Wijmenga, Cisca
    Minster, Ryan L
    Lederer, David J
    Pekkanen, Juha
    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.
    Campbell, Harry
    Morris, Andrew P
    Gläser, Sven
    Hammond, Christopher J
    Burkart, Kristin M
    Beilby, John
    Kritchevsky, Stephen B
    Gudnason, Vilmundur
    Hancock, Dana B
    Williams, O Dale
    Polasek, Ozren
    Zemunik, Tatijana
    Kolcic, Ivana
    Petrini, Marcy F
    Wjst, Matthias
    Kim, Woo Jin
    Porteous, David J
    Scotland, Generation
    Smith, Blair H
    Viljanen, Anne
    Heliövaara, Markku
    Attia, John R
    Sayers, Ian
    Hampel, Regina
    Gieger, Christian
    Deary, Ian J
    Boezen, H Marike
    Newman, Anne
    Jarvelin, Marjo-Riitta
    Wilson, James F
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Stricker, Bruno H
    Teumer, Alexander
    Spector, Timothy D
    Melén, Erik
    Peters, Marjolein J
    Lange, Leslie A
    Barr, R Graham
    Bracke, Ken R
    Verhamme, Fien M
    Sung, Joohon
    Hiemstra, Pieter S
    Cassano, Patricia A
    Sood, Akshay
    Hayward, Caroline
    Dupuis, Josée
    Hall, Ian P
    Brusselle, Guy G
    Tobin, Martin D
    London, Stephanie J
    Genome-wide association analysis identifies six new loci associated with forced vital capacity2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, p. 669-677Article in journal (Refereed)
    Abstract [en]

    Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

  • 169.
    Love-Gregory, Latisha
    et al.
    Washington Univ, Sch Med, Dept Med, Ctr Human Nutr, St Louis, MO 63110 USA..
    Kraja, Aldi T.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA..
    Allum, Fiona
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada..
    Aslibekyan, Stella
    Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA..
    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.
    Duan, Yanan
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA..
    Arnett, Donna K.
    Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35294 USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7JU, England.;Churchill Hosp, Oxford Natl Inst Hlth Res, Biomed Res Ctr, Oxford OX3 7JU, England..
    Deloukas, Panos
    Queen Mary Univ London, William Harvey Res Inst, London EC1M 6BQ, England..
    Ordovas, Jose M.
    Tufts Univ, JM USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA..
    Hopkins, Paul N.
    Univ Utah, Cardiovasc Genet Res, Salt Lake City, UT 84132 USA..
    Grundberg, Elin
    McGill Univ, Dept Human Genet, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada..
    Abumrad, Nada A.
    Washington Univ, Sch Med, Dept Med, Ctr Human Nutr, St Louis, MO 63110 USA..
    Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD362016In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 57, no 12, p. 2176-2184Article in journal (Refereed)
    Abstract [en]

    Cluster of differentiation 36 (CD36) variants influence fasting lipids and risk of metabolic syndrome, but their impact on postprandial lipids, an independent risk factor for cardiovascular disease, is unclear. We determined the effects of SNPs within a approximate to 410 kb region encompassing CD36 and its proximal and distal promoters on chylomicron (CM) remnants and LDL particles at fasting and at 3.5 and 6 h following a high-fat meal (Genetics of Lipid Lowering Drugs and Diet Network study, n = 1,117). Five promoter variants associated with CMs, four with delayed TG clearance and five with LDL particle number. To assess mechanisms underlying the associations, we queried expression quantitative trait loci, DNA methylation, and ChIP-seq datasets for adipose and heart tissues that function in postprandial lipid clearance. Several SNPs that associated with higher serum lipids correlated with lower adipose and heart CD36 mRNA and aligned to active motifs for PPAR, a major CD36 regulator. The SNPs also associated with DNA methylation sites that related to reduced CD36 mRNA and higher serum lipids, but mixed-model analyses indicated that the SNPs and methylation independently influence CD36 mRNA. The findings support contributions of CD36 SNPs that reduce adipose and heart CD36 RNA expression to inter-individual variability of postprandial lipid metabolism and document changes in CD36 DNA methylation that influence both CD36 expression and lipids.

  • 170. Lu, Yingchang
    et al.
    Day, Felix R
    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.
    Buchkovich, Martin L
    Na, Jianbo
    Bataille, Veronique
    Cousminer, Diana L
    Dastani, Zari
    Drong, Alexander W
    Esko, Tõnu
    Evans, David M
    Falchi, Mario
    Feitosa, Mary F
    Ferreira, Teresa
    Hedman, Åsa K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Haring, Robin
    Hysi, Pirro G
    Iles, Mark M
    Justice, Anne E
    Kanoni, Stavroula
    Lagou, Vasiliki
    Li, Rui
    Li, Xin
    Locke, Adam
    Lu, Chen
    Mägi, Reedik
    Perry, John R B
    Pers, Tune H
    Qi, Qibin
    Sanna, Marianna
    Schmidt, Ellen M
    Scott, William R
    Shungin, Dmitry
    Teumer, Alexander
    Vinkhuyzen, Anna A E
    Walker, Ryan W
    Westra, Harm-Jan
    Zhang, Mingfeng
    Zhang, Weihua
    Zhao, Jing Hua
    Zhu, Zhihong
    Afzal, Uzma
    Ahluwalia, Tarunveer Singh
    Bakker, Stephan J L
    Bellis, Claire
    Bonnefond, Amélie
    Borodulin, Katja
    Buchman, Aron S
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Choh, Audrey C
    Choi, Hyung Jin
    Curran, Joanne E
    de Groot, Lisette C P G M
    De Jager, Philip L
    Dhonukshe-Rutten, Rosalie A M
    Enneman, Anke W
    Eury, Elodie
    Evans, Daniel S
    Forsen, Tom
    Friedrich, Nele
    Fumeron, Frédéric
    Garcia, Melissa E
    Gärtner, Simone
    Han, Bok-Ghee
    Havulinna, Aki S
    Hayward, Caroline
    Hernandez, Dena
    Hillege, Hans
    Ittermann, Till
    Kent, Jack W
    Kolcic, Ivana
    Laatikainen, Tiina
    Lahti, Jari
    Mateo Leach, Irene
    Lee, Christine G
    Lee, Jong-Young
    Liu, Tian
    Liu, Youfang
    Lobbens, Stéphane
    Loh, Marie
    Lyytikäinen, Leo-Pekka
    Medina-Gomez, Carolina
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nalls, Mike A
    Nielson, Carrie M
    Oozageer, Laticia
    Pascoe, Laura
    Paternoster, Lavinia
    Polašek, Ozren
    Ripatti, Samuli
    Sarzynski, Mark A
    Shin, Chan Soo
    Narančić, Nina Smolej
    Spira, Dominik
    Srikanth, Priya
    Steinhagen-Thiessen, Elisabeth
    Sung, Yun Ju
    Swart, Karin M A
    Taittonen, Leena
    Tanaka, Toshiko
    Tikkanen, Emmi
    van der Velde, Nathalie
    van Schoor, Natasja M
    Verweij, Niek
    Wright, Alan F
    Yu, Lei
    Zmuda, Joseph M
    Eklund, Niina
    Forrester, Terrence
    Grarup, Niels
    Jackson, Anne U
    Kristiansson, Kati
    Kuulasmaa, Teemu
    Kuusisto, Johanna
    Lichtner, Peter
    Luan, Jian'an
    Mahajan, Anubha
    Männistö, Satu
    Palmer, Cameron D
    Ried, Janina S
    Scott, Robert A
    Stancáková, Alena
    Wagner, Peter J
    Demirkan, Ayse
    Döring, Angela
    Gudnason, Vilmundur
    Kiel, Douglas P
    Kühnel, Brigitte
    Mangino, Massimo
    Mcknight, Barbara
    Menni, Cristina
    O'Connell, Jeffrey R
    Oostra, Ben A
    Shuldiner, Alan R
    Song, Kijoung
    Vandenput, Liesbeth
    van Duijn, Cornelia M
    Vollenweider, Peter
    White, Charles C
    Boehnke, Michael
    Boettcher, Yvonne
    Cooper, Richard S
    Forouhi, Nita G
    Gieger, Christian
    Grallert, Harald
    Hingorani, Aroon
    Jørgensen, Torben
    Jousilahti, Pekka
    Kivimaki, Mika
    Kumari, Meena
    Laakso, Markku
    Langenberg, Claudia
    Linneberg, Allan
    Luke, Amy
    Mckenzie, Colin A
    Palotie, Aarno
    Pedersen, Oluf
    Peters, Annette
    Strauch, Konstantin
    Tayo, Bamidele O
    Wareham, Nicholas J
    Bennett, David A
    Bertram, Lars
    Blangero, John
    Blüher, Matthias
    Bouchard, Claude
    Campbell, Harry
    Cho, Nam H
    Cummings, Steven R
    Czerwinski, Stefan A
    Demuth, Ilja
    Eckardt, Rahel
    Eriksson, Johan G
    Ferrucci, Luigi
    Franco, Oscar H
    Froguel, Philippe
    Gansevoort, Ron T
    Hansen, Torben
    Harris, Tamara B
    Hastie, Nicholas
    Heliövaara, Markku
    Hofman, Albert
    Jordan, Joanne M
    Jula, Antti
    Kähönen, Mika
    Kajantie, Eero
    Knekt, Paul B
    Koskinen, Seppo
    Kovacs, Peter
    Lehtimäki, Terho
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Liu, Yongmei
    Orwoll, Eric S
    Osmond, Clive
    Perola, Markus
    Pérusse, Louis
    Raitakari, Olli T
    Rankinen, Tuomo
    Rao, D C
    Rice, Treva K
    Rivadeneira, Fernando
    Rudan, Igor
    Salomaa, Veikko
    Sørensen, Thorkild I A
    Stumvoll, Michael
    Tönjes, Anke
    Towne, Bradford
    Tranah, Gregory J
    Tremblay, Angelo
    Uitterlinden, André G
    van der Harst, Pim
    Vartiainen, Erkki
    Viikari, Jorma S
    Vitart, Veronique
    Vohl, Marie-Claude
    Völzke, Henry
    Walker, Mark
    Wallaschofski, Henri
    Wild, Sarah
    Wilson, James F
    Yengo, Loïc
    Bishop, D Timothy
    Borecki, Ingrid B
    Chambers, John C
    Cupples, L Adrienne
    Dehghan, Abbas
    Deloukas, Panos
    Fatemifar, Ghazaleh
    Fox, Caroline
    Furey, Terrence S
    Franke, Lude
    Han, Jiali
    Hunter, David J
    Karjalainen, Juha
    Karpe, Fredrik
    Kaplan, Robert C
    Kooner, Jaspal S
    McCarthy, Mark I
    Murabito, Joanne M
    Morris, Andrew P
    Bishop, Julia A N
    North, Kari E
    Ohlsson, Claes
    Ong, Ken K
    Prokopenko, Inga
    Richards, J Brent
    Schadt, Eric E
    Spector, Tim D
    Widén, Elisabeth
    Willer, Cristen J
    Yang, Jian
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Mohlke, Karen L
    Hirschhorn, Joel N
    Pospisilik, John Andrew
    Zillikens, M Carola
    Lindgren, Cecilia
    Kilpeläinen, Tuomas Oskari
    Loos, Ruth J F
    New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk2016In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, article id 10495Article in journal (Refereed)
    Abstract [en]

    To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 individuals. Twelve loci reached genome-wide significance (P<5 × 10(-8)), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14, IGF2BP1, PLA2G6, CRTC1) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.

  • 171. Luis, Desiree
    et al.
    Huang, Xiaoyan
    Sjögren, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Risérus, Ulf
    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.
    Lindholm, Bengt
    Cederholm, Tommy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Carrero, Juan Jesus
    Renal function associates with energy intake in elderly community-dwelling men2014In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 111, no 12, p. 2184-2189Article in journal (Refereed)
    Abstract [en]

    Energy intake and renal function decrease with age. In patients with chronic kidney disease (CKD), spontaneous food intake decreases in parallel with the loss of renal function. The objective of the present study was to evaluate a possible relationship between renal dysfunction and energy intake in elderly community-dwelling men. A cross-sectional study including 1087 men aged 70 years from the Uppsala Longitudinal Study of Adult Men (ULSAM) community-based cohort was carried out. Dietary intake was assessed using 7 d food records, and glomerular filtration rate was estimated from serum cystatin C concentrations. Energy intake was normalised by ideal body weight, and macronutrient intake was energy-adjusted. The median normalised daily energy intake was 105 (interquartile range 88-124) kJ, and directly correlated with estimated glomerular filtration rate (eGFR) as determined by univariate analysis. Across the decreasing quartiles of eGFR, a significant trend of decreasing normalised energy intake was observed (P = 0.01). A multivariable regression model including lifestyle factors and co-morbidities was used for predicting total energy intake. In this model, regular physical activity (standardised beta = 0.160; P = 0.008), smoking (standardised beta = -0.081; P = 0.008), hypertension (standardised beta = -0.097; P = 0.002), hyperlipidaemia (standardised beta = -0.064; P = 0.037) and eGFR (per SD increase, standardised beta = 0.064; P = 0.04) were found to be independent predictors of energy intake. Individuals with manifest CKD (eGFR < 60 ml/min per 1.73m(2)) were more likely to have lower energy intake than those without. In conclusion, there was a direct and independent correlation between renal function and energy intake in a population-based cohort of elderly men. We speculate on a possible link between renal dysfunction and malnutrition in the elderly.

  • 172.
    Lytsy, Per
    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, 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.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Interplay of overweight and insulin resistance on hypertension development2014In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 32, no 4, p. 834-839Article in journal (Refereed)
    Abstract [en]

    Objectives: Obesity and hypertension are associated, possibly through causal pathways involving insulin resistance and metabolic derangements. We aimed to investigate in a whites sample if overweight or obese persons without insulin resistance are at risk of developing hypertension or blood pressure progression. Methods: In a meta-analysis, using multivariable-adjusted mixed-effects logistic regression models, we investigated the risks of hypertension development and blood pressure progression by combinations of relative weight classes and presence or absence of insulin resistance (defined as highest vs. lower three quartiles using the homeostatic model assessment method) in the Uppsala Longitudinal Study of Adult Men (n = 2322) and the Prospective Investigation of the Vasculature in Uppsala Seniors studies (n = 1066). These two samples, consisting mainly of middle-aged and elderly men, provided 1846 observations for the development of hypertension in normotensive individuals and 4223 observations for progressing to a higher blood pressure stage. Results: During a median of 10 years of follow-up, 884 (47.9%) developed hypertension and 1639 (38.8%) progressed to a higher blood pressure stage. Overweight or obese persons without insulin resistance had an increased risk of hypertension development [odds ratio (OR) 1.46, 95% confidence interval 1.14-1.88] and blood pressure progression (OR 1.32, 1.10-1.59) compared with normal-weight persons without insulin resistance. Conclusion: According to this study, being overweight or obese without insulin resistance increases the risk of hypertension and blood pressure progression. This adds to the evidence that overweight and obesity may be harmful per se, and that overweight and obesity without glucometabolic derangements are not benign conditions.

  • 173.
    Ma, Jiantao
    et al.
    NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA;Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;Tufts Univ, Nutr Data Sci, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
    Nano, Jana
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol, Neuherberg, Germany;German Ctr Diabet Res, Munich, Germany.
    Ding, Jingzhong
    Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
    Zheng, Yinan
    Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
    Hennein, Rachel
    NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA;Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.
    Liu, Chunyu
    NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA;Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;Boston Univ, Dept Biostat, Boston, MA 02215 USA.
    Speliotes, Elizabeth K.
    Univ Michigan, Sch Med, Ann Arbor, MI USA.
    Huan, Tianxiao
    NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA;Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.
    Song, Ci
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA;Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.
    Mendelson, Michael M.
    NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA;Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA;Harvard Med Sch, Dept Cardiol, Boston Childrens Hosp, Boston, MA 02115 USA.
    Joehanes, Roby
    NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA;Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.
    Long, Michelle T.
    Boston Univ, Sch Med, Dept Med, Gastroenterol Sect, Boston, MA 02118 USA.
    Liang, Liming
    Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA;Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Smith, Jennifer A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Reynolds, Lindsay M.
    Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
    Ghanbari, Mohsen
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Mashhad Univ Med Sci, Sch Med, Dept Genet, Mashhad, Razavi Khorasan, Iran.
    Muka, Taulant
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    van Meurs, Joyce B. J.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
    Alferink, Louise J. M.
    Erasmus MC, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands.
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
    Dehghan, Abbas
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands;Imperial Coll London, Dept Biostat & Epidemiol, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London, England.
    Ratliff, Scott
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Zhao, Wei
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Bielak, Lawrence
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Kardia, Sharon L. R.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Peyser, Patricia A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Ning, Hongyan
    Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
    VanWagner, Lisa B.
    Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA;Northwestern Univ, Dept Med, Feinberg Sch Med, Div Gastroenterol & Hepatol, Chicago, IL 60611 USA.
    Lloyd-Jones, Donald M.
    Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
    Carr, John Jeffrey
    Vanderbilt Univ, Med Ctr, Dept Radiol & Radiol Sci, Nashville, TN 37232 USA.
    Greenland, Philip
    Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
    Lichtenstein, Alice H.
    Tufts Univ, USDA, Human Nutr Res Ctr Aging, Cardiovasc Nutr Lab, Boston, MA 02111 USA.
    Hu, Frank B.
    Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA USA.
    Liu, Yongmei
    Wake Forest Sch Med, Dept Epidemiol & Prevent, Winston Salem, NC USA.
    Hou, Lifang
    Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
    Murad, Sarwa Darwish
    Erasmus MC, Dept Gastroenterol & Hepatol, Rotterdam, Netherlands.
    Levy, Daniel
    NHLBI, Populat Sci Branch, NIH, Bldg 10, Bethesda, MD 20892 USA;Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.
    A Peripheral Blood DNA Methylation Signature of Hepatic Fat Reveals a Potential Causal Pathway for Nonalcoholic Fatty Liver Disease2019In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 68, no 5, p. 1073-1083Article in journal (Refereed)
    Abstract [en]

    Nonalcoholic fatty liver disease (NAFLD) is a risk factor for type 2 diabetes (T2D). We aimed to identify the peripheral blood DNA methylation signature of hepatic fat. We conducted epigenome-wide association studies of hepatic fat in 3,400 European ancestry (EA) participants and in 401 Hispanic ancestry and 724 African ancestry participants from four population-based cohort studies. Hepatic fat was measured using computed tomography or ultrasound imaging and DNA methylation was assessed at >400,000 cytosine-guanine dinucleotides (CpGs) in whole blood or CD14+ monocytes using a commercial array. We identified 22 CpGs associated with hepatic fat in EA participants at a false discovery rate <0.05 (corresponding P = 6.9 x 10(-6)) with replication at Bonferroni-corrected P < 8.6 x 10(-4). Mendelian randomization analyses supported the association of hypomethylation of cg08309687 (LINC00649) with NAFLD (P = 2.5 x 10(-4)). Hypomethylation of the same CpG was also associated with risk for new-onset T2D (P = 0.005). Our study demonstrates that a peripheral blood-derived DNA methylation signature is robustly associated with hepatic fat accumulation. The hepatic fat-associated CpGs may represent attractive biomarkers for T2D. Future studies are warranted to explore mechanisms and to examine DNA methylation signatures of NAFLD across racial/ethnic groups.

  • 174. Maddock, Jane
    et al.
    Zhou, Ang
    Cavadino, Alana
    Kuźma, Elżbieta
    Bao, Yanchun
    Smart, Melissa C
    Saum, Kai-Uwe
    Schöttker, Ben
    Engmann, Jorgen
    Kjærgaard, Marie
    Karhunen, Ville
    Zhan, Yiqiang
    Lehtimäki, Terho
    Rovio, Suvi P
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lahti, Jari
    Marques-Vidal, Pedro
    Sen, Abhijit
    Perna, Laura
    Schirmer, Henrik
    Singh-Manoux, Archana
    Auvinen, Juha
    Hutri-Kähönen, Nina
    Kähönen, Mika
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Räikkönen, Katri
    Melhus, Håkan
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Guessous, Idris
    Petrovic, Katja E
    Schmidt, Helena
    Schmidt, Reinhold
    Vollenweider, Peter
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Eriksson, Johan G
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Raitakari, Olli T
    Hägg, Sara
    Pedersen, Nancy L
    Herzig, Karl-Heinz
    Järvelin, Marjo-Riitta
    Veijola, Juha
    Kivimaki, Mika
    Jorde, Rolf
    Brenner, Hermann
    Kumari, Meena
    Power, Chris
    Llewellyn, David J
    Hyppönen, Elina
    Vitamin D and cognitive function: A Mendelian randomisation study.2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 13230Article in journal (Refereed)
    Abstract [en]

    The causal nature of the association between hypovitaminosis D and poor cognitive function in mid- to later-life is uncertain. Using a Mendelian randomisation(MR) approach, we examined the causal relationship between 25(OH)D and cognitive function. Data came from 172,349 participants from 17 cohorts. DHCR7(rs12785878), CYP2R1 rs12794714) and their combined synthesis score were chosen to proxy 25(OH)D. Cognitive tests were standardised into global and memory scores. Analyses were stratified by 25(OH)D tertiles, sex and age. Random effects meta-analyses assessed associations between 25(OH)D and cognitive function. Associations of serum 25(OH)D with global and memory-related cognitive function were non-linear (lower cognitive scores for both low and high 25(OH)D, p curvature ≤ 0.006), with much of the curvature attributed to a single study. DHCR7, CYP2R1, and the synthesis score were associated with small reductions in 25(OH)D per vitamin D-decreasing allele. However, coefficients for associations with global or memory-related cognitive function were non-significant and in opposing directions for DHCR7 and CYP2R1, with no overall association observed for the synthesis score. Coefficients for the synthesis score and global and memory cognition were similar when stratified by 25(OH)D tertiles, sex and age. We found no evidence for serum 25(OH)D concentration as a causal factor for cognitive performance in mid- to later life.

  • 175. Mahajan, Anubha
    et al.
    Go, Min Jin
    Zhang, Weihua
    Below, Jennifer E
    Gaulton, Kyle J
    Ferreira, Teresa
    Horikoshi, Momoko
    Johnson, Andrew D
    Ng, Maggie C Y
    Prokopenko, Inga
    Saleheen, Danish
    Wang, Xu
    Zeggini, Eleftheria
    Abecasis, Goncalo R
    Adair, Linda S
    Almgren, Peter
    Atalay, Mustafa
    Aung, Tin
    Baldassarre, Damiano
    Balkau, Beverley
    Bao, Yuqian
    Barnett, Anthony H
    Barroso, Ines
    Basit, Abdul
    Been, Latonya F
    Beilby, John
    Bell, Graeme I
    Benediktsson, Rafn
    Bergman, Richard N
    Boehm, Bernhard O
    Boerwinkle, Eric
    Bonnycastle, Lori L
    Burtt, Noel
    Cai, Qiuyin
    Campbell, Harry
    Carey, Jason
    Cauchi, Stephane
    Caulfield, Mark
    Chan, Juliana C N
    Chang, Li-Ching
    Chang, Tien-Jyun
    Chang, Yi-Cheng
    Charpentier, Guillaume
    Chen, Chien-Hsiun
    Chen, Han
    Chen, Yuan-Tsong
    Chia, Kee-Seng
    Chidambaram, Manickam
    Chines, Peter S
    Cho, Nam H
    Cho, Young Min
    Chuang, Lee-Ming
    Collins, Francis S
    Cornelis, Marilyn C
    Couper, David J
    Crenshaw, Andrew T
    van Dam, Rob M
    Danesh, John
    Das, Debashish
    de Faire, Ulf
    Dedoussis, George
    Deloukas, Panos
    Dimas, Antigone S
    Dina, Christian
    Doney, Alex S F
    Donnelly, Peter J
    Dorkhan, Mozhgan
    van Duijn, Cornelia
    Dupuis, Josee
    Edkins, Sarah
    Elliott, Paul
    Emilsson, Valur
    Erbel, Raimund
    Eriksson, Johan G
    Escobedo, Jorge
    Esko, Tonu
    Eury, Elodie
    Florez, Jose C
    Fontanillas, Pierre
    Forouhi, Nita G
    Forsen, Tom
    Fox, Caroline
    Fraser, Ross M
    Frayling, Timothy M
    Froguel, Philippe
    Frossard, Philippe
    Gao, Yutang
    Gertow, Karl
    Gieger, Christian
    Gigante, Bruna
    Grallert, Harald
    Grant, George B
    Groop, Leif C
    Groves, Christopher J
    Grundberg, Elin
    Guiducci, Candace
    Hamsten, Anders
    Han, Bok-Ghee
    Hara, Kazuo
    Hassanali, Neelam
    Hattersley, Andrew T
    Hayward, Caroline
    Hedman, Asa K
    Herder, Christian
    Hofman, Albert
    Holmen, Oddgeir L
    Hovingh, Kees
    Hreidarsson, Astradur B
    Hu, Cheng
    Hu, Frank B
    Hui, Jennie
    Humphries, Steve E
    Hunt, Sarah E
    Hunter, David J
    Hveem, Kristian
    Hydrie, Zafar I
    Ikegami, Hiroshi
    Illig, Thomas
    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.
    Islam, Muhammed
    Isomaa, Bo
    Jackson, Anne U
    Jafar, Tazeen
    James, Alan
    Jia, Weiping
    Jockel, Karl-Heinz
    Jonsson, Anna
    Jowett, Jeremy B M
    Kadowaki, Takashi
    Kang, Hyun Min
    Kanoni, Stavroula
    Kao, Wen Hong L
    Kathiresan, Sekar
    Kato, Norihiro
    Katulanda, Prasad
    Keinanen-Kiukaanniemi, Sirkka M
    Kelly, Ann M
    Khan, Hassan
    Khaw, Kay-Tee
    Khor, Chiea-Chuen
    Kim, Hyung-Lae
    Kim, Sangsoo
    Kim, Young Jin
    Kinnunen, Leena
    Klopp, Norman
    Kong, Augustine
    Korpi-Hyovalti, Eeva
    Kowlessur, Sudhir
    Kraft, Peter
    Kravic, Jasmina
    Kristensen, Malene M
    Krithika, S
    Kumar, Ashish
    Kumate, Jesus
    Kuusisto, Johanna
    Kwak, Soo Heon
    Laakso, Markku
    Lagou, Vasiliki
    Lakka, Timo A
    Langenberg, Claudia
    Langford, Cordelia
    Lawrence, Robert
    Leander, Karin
    Lee, Jen-Mai
    Lee, Nanette R
    Li, Man
    Li, Xinzhong
    Li, Yun
    Liang, Junbin
    Liju, Samuel
    Lim, Wei-Yen
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, Cecilia M
    Lindholm, Eero
    Liu, Ching-Ti
    Liu, Jian Jun
    Lobbens, Stephane
    Long, Jirong
    Loos, Ruth J F
    Lu, Wei
    Luan, Jian'an
    Lyssenko, Valeriya
    Ma, Ronald C W
    Maeda, Shiro
    Magi, Reedik
    Mannisto, Satu
    Matthews, David R
    Meigs, James B
    Melander, Olle
    Metspalu, Andres
    Meyer, Julia
    Mirza, Ghazala
    Mihailov, Evelin
    Moebus, Susanne
    Mohan, Viswanathan
    Mohlke, Karen L
    Morris, Andrew D
    Muhleisen, Thomas W
    Muller-Nurasyid, Martina
    Musk, Bill
    Nakamura, Jiro
    Nakashima, Eitaro
    Navarro, Pau
    Ng, Peng-Keat
    Nica, Alexandra C
    Nilsson, Peter M
    Njolstad, Inger
    Nothen, Markus M
    Ohnaka, Keizo
    Ong, Twee Hee
    Owen, Katharine R
    Palmer, Colin N A
    Pankow, James S
    Park, Kyong Soo
    Parkin, Melissa
    Pechlivanis, Sonali
    Pedersen, Nancy L
    Peltonen, Leena
    Perry, John R B
    Peters, Annette
    Pinidiyapathirage, Janani M
    Platou, Carl G P
    Potter, Simon
    Price, Jackie F
    Qi, Lu
    Radha, Venkatesan
    Rallidis, Loukianos
    Rasheed, Asif
    Rathmann, Wolfgang
    Rauramaa, Rainer
    Raychaudhuri, Soumya
    Rayner, N William
    Rees, Simon D
    Rehnberg, Emil
    Ripatti, Samuli
    Robertson, Neil
    Roden, Michael
    Rossin, Elizabeth J
    Rudan, Igor
    Rybin, Denis
    Saaristo, Timo E
    Salomaa, Veikko
    Saltevo, Juha
    Samuel, Maria
    Sanghera, Dharambir K
    Saramies, Jouko
    Scott, James
    Scott, Laura J
    Scott, Robert A
    Segre, Ayellet V
    Sehmi, Joban
    Sennblad, Bengt
    Shah, Nabi
    Shah, Sonia
    Shera, A Samad
    Shu, Xiao Ou
    Shuldiner, Alan R
    Sigurðsson, Gunnar
    Sijbrands, Eric
    Silveira, Angela
    Sim, Xueling
    Sivapalaratnam, Suthesh
    Small, Kerrin S
    So, Wing Yee
    Stancakova, Alena
    Stefansson, Kari
    Steinbach, Gerald
    Steinthorsdottir, Valgerdur
    Stirrups, Kathleen
    Strawbridge, Rona J
    Stringham, Heather M
    Sun, Qi
    Suo, Chen
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Takayanagi, Ryoichi
    Takeuchi, Fumihiko
    Tay, Wan Ting
    Teslovich, Tanya M
    Thorand, Barbara
    Thorleifsson, Gudmar
    Thorsteinsdottir, Unnur
    Tikkanen, Emmi
    Trakalo, Joseph
    Tremoli, Elena
    Trip, Mieke D
    Tsai, Fuu Jen
    Tuomi, Tiinamaija
    Tuomilehto, Jaakko
    Uitterlinden, Andre G
    Valladares-Salgado, Adan
    Vedantam, Sailaja
    Veglia, Fabrizio
    Voight, Benjamin F
    Wang, Congrong
    Wareham, Nicholas J
    Wennauer, Roman
    Wickremasinghe, Ananda R
    Wilsgaard, Tom
    Wilson, James F
    Wiltshire, Steven
    Winckler, Wendy
    Wong, Tien Yin
    Wood, Andrew R
    Wu, Jer-Yuarn
    Wu, Ying
    Yamamoto, Ken
    Yamauchi, Toshimasa
    Yang, Mingyu
    Yengo, Loic
    Yokota, Mitsuhiro
    Young, Robin
    Zabaneh, Delilah
    Zhang, Fan
    Zhang, Rong
    Zheng, Wei
    Zimmet, Paul Z
    Altshuler, David
    Bowden, Donald W
    Cho, Yoon Shin
    Cox, Nancy J
    Cruz, Miguel
    Hanis, Craig L
    Kooner, Jaspal
    Lee, Jong-Young
    Seielstad, Mark
    Teo, Yik Ying
    Boehnke, Michael
    Parra, Esteban J
    Chambers, John C
    Tai, E Shyong
    McCarthy, Mark I
    Morris, Andrew P
    Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 3, p. 234-244Article in journal (Refereed)
    Abstract [en]

    To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

  • 176.
    Mahajan, Anubha
    et al.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
    Rodan, Aylin R.
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75229 USA.
    Le, Thu H.
    Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
    Gaulton, Kyle J.
    Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
    Haessler, Jeffrey
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
    Stilp, Adrienne M.
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
    Kamatani, Yoichiro
    Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
    Zhu, Gu
    Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
    Sofer, Tamar
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
    Puri, Sanjana
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75229 USA.
    Schellinger, Jeffrey N.
    Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75229 USA.
    Chu, Pei-Lun
    Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
    Cechova, Sylvia
    Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA.
    van Zuydam, Natalie
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. School of Health and Social Studies, Dalarna University, Falun 791 88, Sweden.
    Flessner, Michael F.
    National Institute of Diabetes, Digestive, and Kidney Disease, NIH, Bethesda, MD 20892, USA.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Heath, Andrew C.
    Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, USA.
    Kubo, Michiaki
    Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7BN, UK.
    Madden, Pamela A. F.
    Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, USA.
    Montgomery, Grant W.
    Molecular Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
    Papanicolaou, George J.
    Epidemiology Branch, Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA.
    Reiner, Alex P.
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Thornton, Timothy A.
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
    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. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
    Cai, Jianwen
    Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
    Martin, Nicholas G.
    Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
    Kooperberg, Charles
    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
    Matsuda, Koichi
    Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
    Whitfield, John B.
    Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia.
    Okada, Yukinori
    Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
    Laurie, Cathy C.
    Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England; Department of Biostatistics, University of Liverpool, Liverpool L69 3GL, UK.
    Franceschini, Nora
    Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27514, USA.
    Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity2016In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 99, no 3, p. 636-646Article in journal (Refereed)
    Abstract [en]

    We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans.

  • 177. Mahajan, Anubha
    et al.
    Sim, Xueling
    Ng, Hui Jin
    Manning, Alisa
    Rivas, Manuel A
    Highland, Heather M
    Locke, Adam E
    Grarup, Niels
    Im, Hae Kyung
    Cingolani, Pablo
    Flannick, Jason
    Fontanillas, Pierre
    Fuchsberger, Christian
    Gaulton, Kyle J
    Teslovich, Tanya M
    Rayner, N William
    Robertson, Neil R
    Beer, Nicola L
    Rundle, Jana K
    Bork-Jensen, Jette
    Ladenvall, Claes
    Blancher, Christine
    Buck, David
    Buck, Gemma
    Burtt, Noël P
    Gabriel, Stacey
    Gjesing, Anette P
    Groves, Christopher J
    Hollensted, Mette
    Huyghe, Jeroen R
    Jackson, Anne U
    Jun, Goo
    Justesen, Johanne Marie
    Mangino, Massimo
    Murphy, Jacquelyn
    Neville, Matt
    Onofrio, Robert
    Small, Kerrin S
    Stringham, Heather M
    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.
    Trakalo, Joseph
    Abecasis, Goncalo
    Bell, Graeme I
    Blangero, John
    Cox, Nancy J
    Duggirala, Ravindranath
    Hanis, Craig L
    Seielstad, Mark
    Wilson, James G
    Christensen, Cramer
    Brandslund, Ivan
    Rauramaa, Rainer
    Surdulescu, Gabriela L
    Doney, Alex S F
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Linneberg, Allan
    Isomaa, Bo
    Tuomi, Tiinamaija
    Jørgensen, Marit E
    Jørgensen, Torben
    Kuusisto, Johanna
    Uusitupa, Matti
    Salomaa, Veikko
    Spector, Timothy D
    Morris, Andrew D
    Palmer, Colin N A
    Collins, Francis S
    Mohlke, Karen L
    Bergman, Richard N
    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.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Tuomilehto, Jaakko
    Hansen, Torben
    Watanabe, Richard M
    Prokopenko, Inga
    Dupuis, Josee
    Karpe, Fredrik
    Groop, Leif
    Laakso, Markku
    Pedersen, Oluf
    Florez, Jose C
    Morris, Andrew P
    Altshuler, David
    Meigs, James B
    Boehnke, Michael
    McCarthy, Mark I
    Lindgren, Cecilia M
    Gloyn, Anna L
    Identification and Functional Characterization of G6PC2 Coding Variants Influencing Glycemic Traits Define an Effector Transcript at the G6PC2-ABCB11 Locus2015In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, no 1, article id e1004876Article in journal (Refereed)
    Abstract [en]

    Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P<5×10-7) evidence for two loci not previously highlighted by common variant GWAS: GLP1R (p.Ala316Thr, minor allele frequency (MAF)=1.5%) influencing FG levels, and URB2 (p.Glu594Val, MAF = 0.1%) influencing FI levels. Coding variant associations can highlight potential effector genes at (non-coding) GWAS signals. At the G6PC2/ABCB11 locus, we identified multiple coding variants in G6PC2 (p.Val219Leu, p.His177Tyr, and p.Tyr207Ser) influencing FG levels, conditionally independent of each other and the non-coding GWAS signal. In vitro assays demonstrate that these associated coding alleles result in reduced protein abundance via proteasomal degradation, establishing G6PC2 as an effector gene at this locus. Reconciliation of single-variant associations and functional effects was only possible when haplotype phase was considered. In contrast to earlier reports suggesting that, paradoxically, glucose-raising alleles at this locus are protective against type 2 diabetes (T2D), the p.Val219Leu G6PC2 variant displayed a modest but directionally consistent association with T2D risk. Coding variant associations for glycemic traits in GWAS signals highlight PCSK1, RREB1, and ZHX3 as likely effector transcripts. These coding variant association signals do not have a major impact on the trait variance explained, but they do provide valuable biological insights.

  • 178.
    Mahajan, Anubha
    et al.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Taliun, Daniel
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Thurner, Matthias
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Robertson, Neil R.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Torres, Jason M.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.
    Rayner, N. William
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Payne, Anthony J.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England.
    Steinthorsdottir, Valgerdur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Grarup, Niels
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark.
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Schmidt, Ellen M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Wuttke, Matthias
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Dept Biometry Epidemiol & Med Bioinformat, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Sarnowski, Chloe
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Magill, Reedik
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Nano, Jana
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Gieger, Christian
    Helmholtz Zentrum Munchen Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Trompet, Stella
    Leiden Univ, Dept Internal Med, Sect Gerontol & Geriatr, Med Ctr, Leiden, Netherlands;Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    Lecoeur, Cecile
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France.
    Preuss, Michael H.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Prins, Bram Peter
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Guo, Xiuqing
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, LABioMed, Torrance, CA 90509 USA.
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Below, Jennifer E.
    Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Nashville, TN USA.
    Bowden, Donald W.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA.
    Chambers, John Campbell
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Dept Cardiol, Ealing Hosp, Harrow, Middx, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England;Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
    Kim, Young Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Div Genome Res, Chungcheongbuk Do, South Korea.
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA;Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA.
    Petty, Lauren E.
    Vanderbilt Univ, Med Ctr, Vanderbilt Genet Inst, Nashville, TN USA.
    Sim, Xueling
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore.
    Zhang, Weihua
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Dept Cardiol, Ealing Hosp, Harrow, Middx, England.
    Bennett, Amanda J.
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Bork-Jensen, Jette
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark.
    Brummett, Chad M.
    Univ Michigan, Dept Anesthesiol, Med Sch, Ann Arbor, MI 48109 USA.
    Canouil, Mickael
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France.
    Kardt, Kai-Uwe Ec
    Charite Univ Med Berlin, Dept Nephrol & Med Intens Care, Berlin, Germany;Charite Univ Med Berlin, German Chron Kidney Dis Study, Berlin, Germany.
    Fischer, Krista
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Kardia, Sharon L. R.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Kronenberg, Florian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Lall, Kristi
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia;Univ Tartu, Inst Math & Stat, Tartu, Estonia.
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
    Locke, Adam E.
    Washington Univ, Sch Med, McDonnell Genome Inst, St Louis, MO USA;Washington Univ, Sch Med, Dept Med, Div Genom & Bioinformat, St Louis, MO 63110 USA.
    Luan, Jian'an
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Ntalla, Loanna
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London, England.
    Nylander, Vibe
    Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England.
    Schoenherr, Sebastian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Yengo, Loic
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France.
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Brandslund, Ivan
    Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark;Vejle Hosp, Dept Clin Biochem, Vejle, Denmark.
    Christensen, Cramer
    Lillebaelt Hosp Vejle, Med Dept, Vejle, Denmark.
    Dedoussis, George
    Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece.
    Florez, Jose C.
    Harvard Med Sch, Dept Med, Boston, MA USA;Massachusetts Gen Hosp, Diabet Res Ctr, Dept Med, Diabet Unit, Boston, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA.
    Ford, Ian
    Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    France, Oscar H.
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Frayling, Timothy M.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Hackinger, Sophie
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Hattersley, Andrew T.
    Univ Exeter, Med Sch, Exeter, Devon, England.
    Herder, Christian
    German Ctr Diabet Res DZD, Neuherberg, Germany;Heinrich Heine Univ Dusseldorf, German Diabet Ctr, Inst Clin Diabetol, Leibniz Ctr Diabet Res, Dusseldorf, Germany.
    Ikram, M. Arfan
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Jorgensen, Marit E.
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark;Southern Denmark Univ, Natl Inst Publ Hlth, Copenhagen, Denmark.
    Jorgensen, Torben
    Res Ctr Prevent & Hlth, Glostrup, Capital Region, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Aalborg Univ, Fac Med, Aalborg, Denmark.
    Kriebel, Jennifer
    Helmholtz Zentrum Munchen Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Ligthart, Symen
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Univ Oxford, Li Ka Shing Ctr Hlth Informat & Discovery, Big Data Inst, Oxford, England.
    Linneberg, Allan
    Res Ctr Prevent & Hlth, Glostrup, Capital Region, Denmark;Bispebjerg & Frederiksberg Hosp, Ctr Clin Res & Prevent, Frederiksberg, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
    Lyssenko, Valeriya
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Diabet Ctr, Malmo, Sweden;Univ Bergen, KG Jebsen Ctr Diabet Res, Dept Clin Sci, Bergen, Norway.
    Mamakou, Vasiliki
    Univ Athens, Dromokaiteio Psychiat Hosp, Athens, Greece.
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, Munich, Germany;German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance Partner Site, Munich, Germany.
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
    Morris, Andrew D.
    Ninewells Hosp & Med Sch, Clin Res Ctr, Ctr Mol Med, Dundee, Scotland;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Nadkarni, Girish
    Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
    Pankow, James S.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Peters, Annette
    German Ctr Diabet Res DZD, Neuherberg, Germany;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance Partner Site, Munich, Germany;German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Stancakova, Alena
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Strauch, Konstantin
    German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
    Taylor, Kent D.
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, LABioMed, Torrance, CA 90509 USA.
    Thorand, Barbara
    German Ctr Diabet Res DZD, Neuherberg, Germany;German Res Ctr Environm Hlth, Inst Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
    Thorleifsson, Gudmar
    Amgen Inc, deCODE Genet, Reykjavik, Iceland.
    Thorsteinsdottir, Unnur
    Amgen Inc, deCODE Genet, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland;Dasman Diabet Inst, Kuwait, Kuwait;Danube Univ Krems, Dept Neurosci & Prevent Med, Krems, Austria;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.
    Witte, Daniel R.
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark;Danish Diabet Acad, Odense, Denmark.
    Dupuis, Josee
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA;NHLBI, Framingham Heart Stud, Framingham, MA USA.
    Peyser, Patricia A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Loos, Ruth J. F.
    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.
    Froguel, Philippe
    Lille Univ, Lille Pasteur Inst, CNRS, UMR8199, Lille, France;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, 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, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Groop, Leif
    Lund Univ, Dept Clin Sci Diabet & Endocrinol, Diabet Ctr, Malmo, Sweden;Univ Helsinki, FIMM, Helsinki, Finland.
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Collins, Francis S.
    NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
    Jukema, J. Wouter
    Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp & Med Sch, Pat Macpherson Ctr Pharmacogenet & Pharmacogen, Dundee, Scotland.
    Grallert, Harald
    Helmholtz Zentrum Munchen Res Ctr Environm Hlth, Inst Epidemiol, Res Unit Mol Epidemiol, Neuherberg, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Helmholtz Zentrum Munchen, Clin Cooparat Grp Type Diabet 2, Munich, Germany;Tech Univ, Helmholtz Zentrum Munchen, Clin Cooparat Grp, Nutrigen & Type Diabet 2, Munich, Germany.
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Dehghan, Abbas
    Erasmus Univ, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands;Imperial Coll London, Dept Epidemiol & Biostat, London, England;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
    Koettgen, Anna
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Dept Biometry Epidemiol & Med Bioinformat, Freiburg, Germany;Univ Freiburg, Med Ctr, Freiburg, Germany.
    Abecasis, Goncalo R.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Meigs, James B.
    Harvard Med Sch, Dept Med, Boston, MA USA;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Div Gen Internal Med, Boston, MA 02114 USA.
    Rotter, Jerome, I
    Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Pediat, LABioMed, Torrance, CA 90509 USA;Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Dept Med, LABioMed, Torrance, CA 90509 USA.
    Marchini, Jonathan
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Dept Stat, Oxford, England.
    Pedersen, Oluf
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark.
    Hansen, Torben
    Univ Copenhagen, Novo Nordisk Fdn, Fac Hlth & Med Sci, Ctr Basic Metab Res, Copenhagen, Denmark;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark.
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Stefansson, Kari
    Amgen Inc, deCODE Genet, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Gloyn, Anna L.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Morris, Andrew P.
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Tartu, Estonian Genome Ctr, Inst Genom, Tartu, Estonia.
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    McCarthy, Mark, I
    Univ Oxford, Wellcome Ctr Human Genet, Nuffield Dept Med, Oxford, England;Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Radcliffe Dept Med, Oxford, England;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford, England.
    Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps2018In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 11, p. 1505-+Article in journal (Refereed)
    Abstract [en]

    We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci,135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%,14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).

  • 179.
    Mahajan, Anubha
    et al.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
    Wessel, Jennifer
    Indiana Univ, Diabet Translat Res Ctr, Dept Epidemiol, Indianapolis, IN 46204 USA;Indiana Univ, Diabet Translat Res Ctr, Dept Med, Indianapolis, IN 46204 USA.
    Willems, Sara M.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Zhao, Wei
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
    Robertson, Neil R.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
    Chu, Audrey Y.
    Natl Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA;Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA.
    Gan, Wei
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
    Kitajima, Hidetoshi
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
    Taliun, Daniel
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Rayner, N. William
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Guo, Xiuqing
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Li, Man
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA;Univ Utah, Sch Med, Dept Internal Med, Div Nephrol & Hypertens, Salt Lake City, UT USA.
    Jensen, Richard A.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
    Hu, Yao
    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
    Huo, Shaofeng
    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
    Lohman, Kurt K.
    Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Dept Biostatist Sci, Winston Salem, NC USA.
    Zhang, Weihua
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, London, Middx, England.
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
    Prins, Bram Peter
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Flannick, Jason
    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.
    Trubetskoy, Vassily Vladimirovich
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Kravic, Jasmina
    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
    Kim, Young Jin
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Rybin, Denis V.
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
    Yaghootkar, Hanieh
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Mueller-Nurasyid, Martina
    Ludwig Maximilians Univ Munchen, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany;DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Partner Site, Munich, Germany.
    Meidtner, Karina
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, Nuthetal, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Varga, Tibor V.
    Lund Univ, Genet & Mol Epidemiol Unit, Diabet Ctr, Dept Clin Sci, Malmo, Sweden.
    Marten, Jonathan
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
    Li, Jin
    Stanford Univ, Dept Med, Sch Med, Div Cardiovasc Med, Stanford, CA 94305 USA.
    Smith, Albert Vernon
    Iceland Heart Assoc, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    An, Ping
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Ligthart, Symen
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    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.
    Malerba, Giovanni
    Univ Verona, Dept Neurosci Biomed & Movement Sci, Sect Biol & Genet, Verona, Italy.
    Demirkan, Ayse
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
    Tajes, Juan Fernandez
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England.
    Steinthorsdottir, Valgerdur
    deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Wuttke, Matthias
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Med Ctr, Freiburg, Germany.
    Lecoeur, Cecile
    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France.
    Preuss, Michael
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Graff, Marielisa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
    Highland, Heather M.
    Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Human Genet Ctr, Houston, TX 77030 USA.
    Justice, Anne E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
    Liu, Dajiang J.
    Penn State Coll Med, Inst Personalized Med, Dept Publ Hlth Sci, Hershey, PA USA.
    Marouli, Eirini
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
    Peloso, Gina Marie
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
    Warren, Helen R.
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England;Queen Mary Univ London, Natl Inst Hlth Res, Barts Cardiovasc Biomed Res Unit, London, England.
    Afaq, Saima
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.
    Afzal, Shoaib
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Ahlqvist, Emma
    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
    Almgren, Peter
    Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden.
    Amin, Najaf
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Bang, Lia B.
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark.
    Bertoni, Alain G.
    Wake Forest Univ Hlth Sci, Dept Epidemiol & Prevent, Publ Hlth Sci, Winston Salem, NC USA.
    Bombieri, Cristina
    Univ Verona, Dept Neurosci Biomed & Movement Sci, Sect Biol & Genet, Verona, Italy.
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
    Brandslund, Ivan
    Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark;Vejle Hosp, Dept Clin Biochem, Vejle, Denmark.
    Brody, Jennifer A.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
    Burtt, Noel P.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
    Canouil, Mickael
    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France.
    Chen, Yii-Der Ida
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Cho, Yoon Shin
    Hallym Univ, Dept Biomed Sci, Chunchon, South Korea.
    Christensen, Cramer
    Lillebaelt Hosp Vejle, Med Dept, Vejle, Denmark.
    Eastwood, Sophie V.
    UCL, Inst Cardiovasc Sci, London, England.
    Eckardt, Kai-Uwe
    Charite Univ Med Berlin, Dept Nephrol & Med Intens Care, Berlin, Germany.
    Fischer, Krista
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Gambaro, Giovanni
    Univ Cattolica Sacro Cuore, Inst Internal & Geriatr Med, Rome, Italy.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA.
    de Haan, Hugoline G.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Hackinger, Sophie
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Hai, Yang
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Han, Sohee
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Tybjaerg-Hansen, Anne
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark.
    Hivert, Marie-France
    Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA;Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA;Univ Sherbrooke, Dept Med, Sherbrooke, PQ, Canada.
    Isomaa, Bo
    Malmska Municipal Hlth Care Ctr & Hosp, Pietarsaari, Finland;Folkhalsan Res Ctr, Helsinki, Finland.
    Jager, Susanne
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, Nuthetal, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Jorgensen, Marit E.
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark;Southern Denmark Univ, Natl Inst Publ Hlth, Copenhagen, Denmark.
    Jorgensen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Res Ctr Prevent & Hlth, Glostrup, Denmark;Aalborg Univ, Fac Med, Aalborg, Denmark.
    Karajamaki, Annemari
    Vaasa Cent Hosp, Dept Primary Hlth Care, Vaasa, Finland;Vaasa Hlth Care Ctr, Diabet Ctr, Vaasa, Finland.
    Kim, Bong-Jo
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Kim, Sung Soo
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Koistinen, Heikki A.
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland;Helsinki Univ Hosp, Abdominal Ctr, Endocrinol, Helsinki, Finland;Minerva Fdn, Helsinki, Finland;Univ Helsinki, Dept Med, Helsinki, Finland;Univ Helsinki, Cent Hosp, Helsinki, Finland.
    Kovacs, Peter
    Univ Leipzig, Ctr Adipos Dis, Integrated Res & Treatment IFB, Leipzig, Germany.
    Kriebel, Jennifer
    German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Res Unit Mol Epidemiol, Neuherberg, Germany.
    Kronenberg, Florian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Lall, Kristi
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia;Univ Tartu, Inst Math Stat, Tartu, Estonia.
    Lange, Leslie A.
    Univ Colorado Denver, Div Bioinformat & Personalized Med, Dept Med, Aurora, CO USA.
    Lee, Jung-Jin
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
    Lehne, Benjamin
    Imperial Coll London, Dept Epidemiol & Biostat, London, England.
    Li, Huaixing
    Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutrit Sci, Shanghai, Peoples R China.
    Lin, Keng-Hung
    Taichung Vet Gen Hosp, Dept Ophthalmol, Taichung, Taiwan.
    Linneberg, Allan
    Res Ctr Prevent & Hlth, Glostrup, Denmark;Rigshosp, Dept Clin Expt Res, Glostrup, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
    Liu, Ching-Ti
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
    Liu, Jun
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Loh, Marie
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;Univ Oulu, Inst Hlth Sci, Oulu, Finland;ASTAR, TLGM, Singapore, Singapore.
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Mamakou, Vasiliki
    Univ Athens, Dromokaiteio Psychiat Hosp, Athens, Greece.
    McKean-Cowdin, Roberta
    Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
    Nadkarni, Girish
    Icahn Sch Med Mt Sinai, Dept Med, Div Nephrol, New York, NY 10029 USA.
    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, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Ntalla, Ioanna
    Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England.
    Peyser, Patricia A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
    Rathmann, Wolfgang
    German Ctr Diabet Res DZD, Neuherberg, Germany;Univ Dusseldorf, Leibniz Ctr Diabet Res Heinrich Heine, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany.
    Rice, Kenneth
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Rich, Stephen S.
    Univ Virginia, Sch Med, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
    Rode, Line
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark.
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Schonherr, Sebastian
    Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, Div Genet Epidemiol, Innsbruck, Austria.
    Selvin, Elizabeth
    Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
    Small, Kerrin S.
    Kings Coll London, Dept Twins Res & Genet Epidemiol, London, England.
    Stancakova, Alena
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Surendran, Praveen
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
    Taylor, Kent D.
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Teslovich, Tanya M.
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Thorand, Barbara
    German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.
    Thorleifsson, Gudmar
    deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Tin, Adrienne
    Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
    Tonjes, Anke
    Univ Leipzig, Dept Med, Leipzig, Germany.
    Varbo, Anette
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, Copenhagen, Denmark.
    Witte, Daniel R.
    Aarhus Univ, Dept Publ Hlth, Aarhus, Denmark;Danish Diabet Acad, Odense, Denmark.
    Wood, Andrew R.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Yajnik, Pranav
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Yao, Jie
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    Yengo, Loic
    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France.
    Young, Robin
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
    Amouyel, Philippe
    Univ Lille Nord France, INSERM, U1167, Inst Pasteur Lille, Lille, France.
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Epidemiol, Nuthetal, Germany.
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Dept Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Chowdhury, Rajiv
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    Collins, Francis S.
    NHGRI, US Natl Inst Hlth, Genome Technol Branch, Bethesda, MD 20892 USA.
    Dedoussis, George
    Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece.
    Dehghan, Abbas
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England;German Ctr Diabet Res DZD, Neuherberg, Germany;Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Imperial Coll London, MRC PHE Ctr Environm & Hlth, London, England.
    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.
    Ferrario, Marco M.
    Univ Insubria, Dept Med & Surg, Res Ctr Epidemiol & Prevent Med EPIMED, Varese, Italy.
    Ferrieres, Jean
    INSERM, UMR 1027, Toulouse, France;Toulouse Univ, Sch Med, Dept Cardiol, Toulouse, France.
    Florez, Jose C.
    Massachusetts Gen Hosp, Dept Med, Diabet Unit, Diabet Res Ctr, Boston, MA 02114 USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA;Harvard Med Sch, Dept Med, Boston, MA USA.
    Frossard, Philippe
    Ctr Noncommunicable Dis, Karachi, Pakistan.
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Harris, Tamara B.
    US Natl Inst Hlth, Natl Inst Aging, Laboratory Epidemiol & Populat Sci, Bethesda, MD USA.
    Heckbert, Susan R.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Kathiresan, Sekar
    Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA;Harvard Med Sch, Dept Med, Boston, MA USA;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
    Kee, Frank
    Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth NI, Belfast, Antrim, North Ireland.
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio, Finland;Kuopio Univ Hosp, Kuopio, Finland.
    Langenberg, Claudia
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Launer, Lenore J.
    US Natl Inst Hlth, Natl Inst Aging, Laboratory Epidemiol & Populat Sci, Bethesda, MD USA.
    Lindgren, Cecilia M.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford, England.
    Mannisto, Satu
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Meitinger, Thomas
    Tech Univ Munich, Inst Human Genet, Munich, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Human Genet, Neuherberg, Germany.
    Melander, Olle
    Lund Univ, Dept Clin Sci Hypertens & Cardiovasc Dis, Malmo, Sweden.
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
    Moitry, Marie
    Univ Strasbourg, Dept Epidemiol & Publ Hlth, Strasbourg, France;Univ Hosp Strasbourg, Dept Publ Hlth, Strasbourg, France.
    Morris, Andrew D.
    Ninewells Hosp, Ctr Mol Med, Clin Res Ctr, Dundee, Scotland;Med Sch, Dundee, Scotland;Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
    Murray, Alison D.
    Univ Aberdeen, Sch Med Med Sci & Nutr, Aberdeen Biomed Imaging Ctr, Aberdeen, Scotland.
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci Diabet & Cardiovasc Dis, Genet Epidemiol, Malmo, Sweden.
    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.
    Perola, Markus
    Natl Inst Hlth & Welf, Helsinki, Finland;Univ Helsinki, FIMM, Helsinki, Finland.
    Peters, Annette
    DZHK German Ctr Cardiovasc Res, Munich Heart Alliance, Partner Site, Munich, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.
    Province, Michael A.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63110 USA.
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan.
    Ridker, Paul M.
    Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA USA.
    Rivadineira, Fernando
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
    Rosendaal, Frits R.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands.
    Rosengren, Anders H.
    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Sheu, Wayne H. -H.
    Taichung Vet Gen Hosp, Dept Internal Med, Taichung, Taiwan;Natl Yang Ming Univ, Sch Med, Taipei, Taiwan;Sch Med, Natl Def Med Ctr, Taipei, Taiwan.
    Sladek, Rob
    McGill Univ, Montreal, PQ, Canada;Genome Quebec Innovat Ctr, Montreal, PQ, Canada;McGill Univ, Dept Human Genet, Montreal, PQ, Canada;McGill Univ, Dept Med, Div Endocrinol & Metab, Montreal, PQ, Canada.
    Smith, Blair H.
    Univ Dundee, Ninewells Hosp, Div Populat Hlth Sci, Dundee, Scotland;Univ Dundee, Med Sch, Dundee, Scotland.
    Strauch, Konstantin
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, Neuherberg, Germany;Ludwig Maximilians Univ Munchen, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
    Uitterlinden, Andre G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Varma, Rohit
    Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90033 USA.
    Willer, Cristen J.
    Univ Michigan, Div Cardiovasc Med, Dept Internal 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.
    Bluher, Matthias
    Univ Leipzig, Ctr Adipos Dis, Integrated Res & Treatment IFB, Leipzig, Germany;Univ Leipzig, Dept Med, Leipzig, Germany.
    Butterworth, Adam S.
    German Ctr Diabet Res DZD, Neuherberg, Germany;Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England.
    Chambers, John Campbell
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, London, Middx, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England.
    Chasman, Daniel I.
    Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Dept Med, Boston, MA USA.
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England;Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton, England;Univ Cambridge, Dept Med, British Heart Fdn, Cambridge Ctr Excellence, Cambridge, England.
    van Duijn, Cornelia
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Dupuis, Josee
    Natl Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA USA;Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
    Franco, Oscar H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    Franks, Paul W.
    Lund Univ, Genet & Mol Epidemiol Unit, Diabet Ctr, Dept Clin Sci, Malmo, Sweden;Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA USA.
    Froguel, Philippe
    Lille Univ, Lille Pasteur Inst, CNRS, UMR 8199, Lille, France;Imperial Coll London, Sch Publ Hlth, Dept Genom Common Dis, London, England.
    Grallert, Harald
    German Ctr Diabet Res DZD, Neuherberg, Germany;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Res Unit Mol Epidemiol, Neuherberg, Germany;Ludwig Maximillians Univ Munich, Helmholtz Zentrum Munchen, Clin Cooperat Grp Type Diabet 2, Munich, Germany;Tech Univ Munich, Clin Cooperat Grp Nutrigen & Type Diabet 2, Helmholtz Zentrum Munchen, Munich, Germany.
    Groop, Leif
    Lund Univ, Diabet Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden;Univ Helsinki, FIMM, Helsinki, Finland.
    Han, Bok-Ghee
    Korea Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea.
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark;Univ Southern Denmark, Fac Hlth Sci, Odense, Denmark.
    Hattersley, Andrew T.
    Univ Exeter, Med Sch, Exeter, Devon, England.
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, 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.
    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.
    Kooner, Jaspal Singh
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, London, Middx, England;Imperial Coll London, Imperial Coll Healthcare NHS Trust, London, England;Imperial Coll London, Natl Heart & Lung Inst, Cardiovasc Sci, Hammersmith Campus, London, England.
    Kottgen, Anna
    Univ Freiburg, Fac Med, Inst Genet Epidemiol, Med Ctr, Freiburg, Germany.
    Kuulasmaa, Kari
    Tech Univ Munich, Inst Human Genet, Munich, Germany.
    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 Nutrit Sci, Shanghai, Peoples R China.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Liu, Yongmei
    Wake Forest Univ Hlth Sci, Dept Epidemiol & Prevent, Publ Hlth Sci, Winston Salem, NC 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, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
    Marchini, Jonathan
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Oxford, Dept Stat, Oxford, England.
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Mook-Kanamori, Dennis
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands.
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, Herlev, Denmark;Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark;Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen, Denmark.
    Palmer, Colin N. A.
    Univ Dundee, Ninewells Hosp, Pat Macpherson Ctr Pharmacogenet & Pharmacogenom, Dundee, Scotland;Univ Dundee, Med Sch, Dundee, Scotland. Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
    Pankow, James S.
    Harvard Med Sch, Harvard Pilgrim Hlth Care Inst, Dept Populat Med, Boston, MA USA.
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark.
    Psaty, Bruce M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.
    Sattar, Naveed
    Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
    Schulze, Matthias B.
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, Nuthetal, Germany;German Ctr Diabet Res DZD, Neuherberg, Germany.
    Soranzo, Nicole
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England;Univ Cambridge, Sch Clin Med, Dept Hematol, Cambridge, England.
    Spector, Timothy D.
    Kings Coll London, Dept Twins Res & Genet Epidemiol, London, England.
    Stefansson, Kari
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Stumvoll, Michael
    Univ Hosp Leipzig, Div Endocrinol, Leipzig, Germany;Univ Hosp Leipzig, Div Nephrol, Leipzig, Germany.
    Thorsteinsdottir, Unnur
    Univ Iceland, Fac Med, Reykjavik, Iceland;deCODE Genet Amgen Inc, Reykjavik, Iceland.
    Tuomi, Tiinamaija
    Folkhalsan Res Ctr, Helsinki, Finland;Helsinki Univ Hosp, Abdominal Ctr, Endocrinol, Helsinki, Finland;Univ Helsinki, FIMM, Helsinki, Finland;Univ Helsinki, Res Programs Unit, Diabet & Obes, Helsinki, Finland.
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, Dept Hlth, Helsinki, Finland;Dasman Diabet Inst, Dasman, Kuwait;Danube Univ Krems, Dept Neurosci & Prevent Med, Krems, Austria;King Abdulaziz Univ, Diabet Res Grp, Jeddah, Saudi Arabia.
    Wareham, Nicholas J.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England.
    Scott, Robert A.
    Univ Cambridge, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Barroso, Ines
    Wellcome Trust Sanger Inst, Dept Human Genet, Hinxton, England;Univ Cambridge, Wellcome Trust MRC Inst Metab Sci, Metabol Res Labs, Cambridge, England.
    Frayling, Timothy M.
    Univ Exeter, Med Sch, Genet Complex Traits, Exeter, Devon, England.
    Goodarzi, Mark O.
    Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
    Meigs, James B.
    Harvard Med Sch, Dept Med, Boston, MA USA;Harvard Med Sch, Massachusetts Gen Hosp, Gen Med Div, Boston, MA USA.
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
    Saleheen, Danish
    Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA;Ctr Noncommunicable Dis, Karachi, Pakistan.
    Morris, Andrew P.
    Univ Oxford, Nuffield Dept Med, Wellcome Trust Ctr Human Genet, Oxford, England;Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England;Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Rotter, Jerome I.
    Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Pediat,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Univ Calif Los Angeles, Med Ctr, LABioMed Harbor, Dept Med,Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
    McCarthy, Mark I.
    Univ Oxford, Nuffield Dept Med, 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.
    Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes2018In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 4, p. 559-571Article in journal (Refereed)
    Abstract [en]

    We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 x 10(-7)); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio <= 1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.

  • 180.
    Malik, Rainer
    et al.
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany.
    Chauhan, Ganesh
    Indian Inst Sci, Ctr Brain Res, Bangalore, Karnataka, India;Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France.
    Traylor, Matthew
    Univ Cambridge, Div Clin Neurosci, Stroke Res Grp, Cambridge, England.
    Sargurupremraj, Muralidharan
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France;NUI Galway, Dept Med, Clin Res Facil, Galway, Ireland.
    Okada, Yukinori
    RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan;Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan;Osaka Univ, Immunol Frontier Res Ctr WPI IFReC, Lab Stat Immunol, Suita, Osaka, Japan;Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
    Mishra, Aniket
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France.
    Rutten-Jacobs, Loes
    Univ Cambridge, Div Clin Neurosci, Stroke Res Grp, Cambridge, England.
    Giese, Anne-Katrin
    Harvard Med Sch, MGH, Dept Neurol, Boston, MA USA.
    van der Laan, Sander W.
    Univ Utrecht, Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol,Dept Cardiol, Utrecht, Netherlands.
    Gretarsdottir, Solveig
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland.
    Anderson, Christopher D.
    MGH, Ctr Genom Med, Boston, MA USA;MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
    Chong, Michael
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Adams, Hieab H. H.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands;Erasmus Univ, Med Ctr, Dept Radiol & Nucl Med, Rotterdam, Netherlands.
    Ago, Tetsuro
    Kyushu Univ, Grad Sch Med Sci, Dept Med & Clin Sci, Fukuoka, Japan.
    Almgren, Peter
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Amouyel, Philippe
    Univ Lille, Risk Factors & Mol Determinants Aging Related Dis, Inst Pasteur Lille, INSERM,LabEx DISTALZ,UMR1167, Lille, France;CHU Lille, Epidemiol & Publ Hlth Dept, Lille, France.
    Ay, Hakan
    MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA;Harvard Med Sch, MGH, Dept Radiol, AA Martinos Ctr Biomed Imaging, Boston, MA USA.
    Bartz, Traci M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Biostat, Seattle, WA 98195 USA;Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA.
    Benavente, Oscar R.
    Univ British Columbia, Brain Res Ctr, Div Neurol, Fac Med, Vancouver, BC, Canada.
    Bevan, Steve
    Univ Lincoln, Sch Life Sci, Lincoln, England.
    Boncoraglio, Giorgio B.
    IRCCS, Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy.
    Brown, Robert D., Jr.
    Mayo Clin, Dept Neurol, Rochester, MN USA.
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Natl Inst Hlth Res Blood, Cambridge, England;Univ Cambridge, Transplant Res Unit Donor Hlth & Gen, Cambridge, England.
    Carrera, Caty
    Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Neurol Dept, Barcelona, Spain;Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Med Dept, Barcelona, Spain;Fundacio Docencia & Recerca MutuaTerrassa, Stroke Pharmacogen & Genet, Recerca MutuaTerrassa, Terrassa, Spain.
    Carty, Cara L.
    Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC 20010 USA;George Washington Univ, Ctr Translat Sci, Washington, DC USA.
    Chasman, Daniel I.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Chen, Wei-Min
    Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    Cole, John W.
    Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA;Baltimore VAMC, Baltimore, MD USA.
    Correa, Adolfo
    Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA;Univ Mississippi, Med Ctr, Dept Pediat, Jackson, MS 39216 USA;Univ Mississippi, Med Ctr, Dept Populat Hlth Sci, Jackson, MS 39216 USA.
    Cotlarciuc, Ioana
    Royal Holloway Univ London, Inst Cardiovasc Res, London, England;Ashford, Surrey, England;St Peters Hosp, Surrey, England.
    Cruchaga, Carlos
    Washington Univ, Sch Med, Dept Psychiat, Hope Ctr Program Prot Aggregat & Neurodegenerat H, St Louis, MO 63110 USA;Washington Univ, Sch Med, Dept Dev Biol, St Louis, MO USA.
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Univ Cambridge, Dept Publ Hlth & Primary Care, NIHR Blood & Transplant Res Unit Donor Hlth & Gen, Cambridge, England;Wellcome Trust Sanger Inst, Cambridge, England;Univ Cambridge, Dept Med, British Heart Fdn, Cambridge Ctr Excellence, Cambridge, England.
    de Bakker, Paul I. W.
    Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands;Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Dept Epidemiol, Utrecht, Netherlands.
    DeStefano, Anita L.
    Boston Univ, Sch Publ Hlth, Boston, MA USA;Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
    den Hoed, Marcel
    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.
    Duan, Qing
    Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
    Engelter, Stefan T.
    Basel Univ Hosp, Dept Neurol, Basel, Switzerland;Basel Univ Hosp, Stroke Ctr, Basel, Switzerland;Univ Basel, Neurorehabilitat Unit, Basel, Switzerland;Univ Ctr Med Aging & Rehabil Basel, Felix Platter Hosp, Basel, Switzerland.
    Falcone, Guido J.
    Yale Univ, Sch Med, Dept Neurol, New Haven, CT 06510 USA;Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
    Gottesman, Rebecca F.
    Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
    Grewal, Raji P.
    SF Med Ctr, Neurosci Inst, Trenton, NJ USA.
    Gudnason, Vilmundur
    Iceland Heart Assoc Res Inst, Kopavogur, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    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.
    Haessler, Jeffrey
    SF Med Ctr, Neurosci Inst, Trenton, NJ USA.
    Harris, Tamara B.
    NIH, Natl Inst Aging, Lab Epidemiol & Populat Sci, Bldg 10, Bethesda, MD 20892 USA.
    Hassan, Ahamad
    Leeds Teaching Hosp NHS Trust, Leeds Gen Infirm, Dept Neurol, Leeds, W Yorkshire, England.
    Havulinna, Aki S.
    Natl Inst Hlth & Welf, Helsinki, Finland;Inst Mol Med Finland, FIMM, Helsinki, Finland.
    Heckbert, Susan R.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
    Holliday, Elizabeth G.
    Hunter Med Res Inst, Publ Hlth Stream, New Lambton, NSW, Australia;Univ Newcastle, Fac Hlth & Med, Newcastle, NSW, Australia.
    Howard, George
    Univ Alabama Birmingham, Sch Publ Hlth, Birmingham, AL 35294 USA.
    Hsu, Fang-Chi
    Wake Forest Sch Med, Dept Biostat, Winston Salem, NC USA.
    Hyacinth, Hyacinth I.
    Emory Univ, Sch Med, Dept Pediat, Aflac Canc & Blood Disorder Ctr, Atlanta, GA USA.
    Ikram, M. Arfan
    Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
    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, Div Cardiovasc Med, Dept Med, Stanford, CA USA..
    Irvin, Marguerite R.
    Univ Alabama Birmingham, Sch Publ Hlth, Epidemiol, Birmingham, AL 35294 USA.
    Jian, Xueqiu
    Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA.
    Jimenez-Conde, Jordi
    Univ Autonoma Barcelona, Inst Hosp Mar Invest Med, Neurol Dept, Neurovasc Res Grp NEUVAS, Barcelona, Spain.
    Johnson, Julie A.
    Univ Florida, Coll Pharm, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA;Univ Florida, Coll Pharm, Ctr Pharmacogen, Gainesville, FL USA;Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA.
    Jukema, J. Wouter
    Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
    Kanai, Masahiro
    RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan;Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan;Harvard Med Sch, Program Bioinformat & Integrat Gen, Boston, MA USA.
    Keene, Keith L.
    East Carolina Univ, Dept Biol, Greenville, NC USA;East Carolina Univ, Ctr Hlth Dispar, Greenville, NC USA.
    Kissela, Brett M.
    Univ Cincinnati, Coll Med, Cincinnati, OH USA.
    Kleindorfer, Dawn O.
    Univ Cincinnati, Coll Med, Cincinnati, OH USA.
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1124 Columbia St, Seattle, WA 98104 USA.
    Kubo, Michiaki
    RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan.
    Lange, Leslie A.
    Univ Colorado Denver, Dept Med, Anschutz Med Campus, Aurora, CO USA.
    Langefeld, Carl D.
    Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC USA;Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC USA.
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Launer, Lenore J.
    NIH, Natl Inst Aging, Intramural Res Program, Bldg 10, Bethesda, MD 20892 USA.
    Lee, Jin-Moo
    Washington Univ, Sch Med, Dept Neurol Radiol & Biomed Engn, St Louis, MO USA.
    Lemmens, Robin
    Univ Leuven, KU Leuven, Dept Neurosci Expt Neurol, Leuven, Belgium;Univ Hosp Leuven, Dept Neurol, VIB Ctr Brain & Dis Res, Leuven, Belgium.
    Leys, Didier
    Univ Lille, CHU Lille, INSERM, U 1171, Lille, France.
    Lewis, Cathryn M.
    Kings Coll London, Dept Med & Mol Genet, London, England;Kings Coll London, Inst Psychiat Psychol & Neurosci, SGDP Ctr, London, England.
    Lin, Wei-Yu
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England;Newcastle Univ, Northern Inst Canc Res, Newcastle, NSW, Australia.
    Lindgren, Arne G.
    Lund Univ, Dept Clin Sci Lund, Neurol, Lund, Sweden;Skane Univ Hosp, Dept Neurol & Rehabil Med, Lund, Sweden.
    Lorentzen, Erik
    Univ Gothenburg, Bioinformat Core Facil, Gothenburg, Sweden.
    Magnusson, Patrik K.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
    Maguire, Jane
    Univ Technol Sydney, Fac Hlth, Ultimo, NSW, Australia.
    Manichaikul, Ani
    Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    McArdle, Patrick F.
    Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
    Meschia, James F.
    Mayo Clin, Dept Neurol, Jacksonville, FL USA.
    Mitchell, Braxton D.
    Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA;Baltimore Vet Adm, Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA.
    Mosley, Thomas H.
    Univ Mississippi, Med Ctr, Sch Med, Div Geriatr, Jackson, MS 39216 USA;Univ Mississippi, Med Ctr, Memory Impairment & Neurodegenerat Dementia Ctr, Jackson, MS 39216 USA.
    Nalls, Michael A.
    NIH, Natl Inst Aging, Lab Neurogenet, Bldg 10, Bethesda, MD 20892 USA;Data Tecn Int, Glen Echo, MD USA.
    Ninomiya, Toshiharu
    Kyushu Univ, Grad Sch Med Sci, Dept Epidemiol & Publ Hlth, Fukuoka, Japan.
    O'Donnell, Martin J.
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada;NUI Galway, Dept Med, Clin Res Facil, Galway, Ireland.
    Psaty, Bruce M.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA;Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA;Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA.
    Pulit, Sara L.
    Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands;Univ Med Ctr Utrecht, Dept Neurol, Brain Ctr Rudolf Magnus, Utrecht, Netherlands.
    Rannikmae, Kristiina
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland.
    Reiner, Alexander P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA.
    Rexrode, Kathryn M.
    Brigham & Womens Hosp, Dept Med, 75 Francis St, Boston, MA 02115 USA.
    Rice, Kenneth
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
    Rich, Stephen S.
    Univ Virginia, Dept Publ Hlth Sci, Ctr Publ Hlth Genom, Charlottesville, VA USA.
    Ridker, Paul M.
    Brigham & Womens Hosp, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Rost, Natalia S.
    Harvard Med Sch, MGH, Dept Neurol, Boston, MA USA;MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA.
    Rothwell, Peter M.
    Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England.
    Rotter, Jerome I.
    Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Harbor UCLA, Med Ctr, Dept Pediat, Div Genom Outcomes, Torrance, CA USA.
    Rundek, Tatjana
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
    Sacco, Ralph L.
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
    Sakaue, Saori
    Osaka Univ, Grad Sch Med, Dept Stat Genet, Osaka, Japan;Univ Tokyo, Grad Sch Med, Dept Allergy & Rheumatol, Tokyo, Japan.
    Sale, Michele M.
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA.
    Salomaa, Veikko
    Natl Inst Hlth & Welf, Helsinki, Finland.
    Sapkota, Bishwa R.
    Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73190 USA.
    Schmidt, Reinhold
    Med Univ Graz, Dept Neurol, Graz, Austria.
    Schmidt, Carsten O.
    Univ Med Greifswald, SHIP KEF, Inst Community Med, Greifswald, Germany.
    Schminke, Ulf
    Univ Med Greifswald, Dept Neurol, Greifswald, Germany.
    Sharma, Pankaj
    Royal Holloway Univ London, Inst Cardiovasc Res, London, England;Ashford, Surrey, England;St Peters Hosp, Surrey, England.
    Slowik, Agnieszka
    Jagiellonian Univ, Dept Neurol, Krakow, Poland.
    Sudlow, Cathie L. M.
    Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland;Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland.
    Tanislav, Christian
    Justus Liebig Univ, Dept Neurol, Giessen, Germany.
    Tatlisumak, Turgut
    Univ Gothenburg, Sahlgrenska Acad, Inst Neuroscience & Physiol, Dept Clin Neurosci Neurol, Gothenburg, Sweden;Sahlgrens Univ Hosp, Gothenburg, Sweden.
    Taylor, Kent D.
    Univ Calif Los Angeles, Med Ctr, Los Angeles Biomed Res Inst Harbor, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA;Harbor UCLA, Med Ctr, Dept Pediat, Div Genom Outcomes, Torrance, CA USA.
    Thijs, Vincent N. S.
    Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Stroke Div, Heidelberg, Vic, Australia;Austin Hlth, Dept Neurol, Heidelberg, Vic, Australia.
    Thorleifsson, Gudmar
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland.
    Thorsteinsdottir, Unnur
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland.
    Tiedt, Steffen
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany.
    Trompet, Stella
    Leiden Univ, Med Ctr, Sect Gerontol & Geriatr, Dept Internal Med, Leiden, Netherlands.
    Tzourio, Christophe
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Dept Publ Hlth, Bordeaux, France.
    van Duijn, Cornelia M.
    Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands;Ctr Med Syst Biol, Leiden, Netherlands.
    Walters, Matthew
    Univ Glasgow, Sch Med Dent & Nursing, Glasgow, Lanark, Scotland.
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
    Wassertheil-Smoller, Sylvia
    Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
    Wiggins, Kerri L.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    Yang, Qiong
    Boston Univ, Sch Publ Hlth, Boston, MA USA.
    Yusuf, Salim
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Bis, Joshua C.
    Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
    Pastinen, Tomi
    McGill Univ, Dept Human Genet, Montreal, PQ, Canada.
    Ruusalepp, Arno
    Univ Tartu, Inst Biomed & Translat Med, Dept Pathophysiol, Tartu, Estonia;Tartu Univ Hosp, Dept Cardiac Surg, Tartu, Estonia;Clin Gene Networks AB, Stockholm, Sweden.
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Koplev, Simon
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA.
    Bjorkegren, Johan L. M.
    Clin Gene Networks AB, Stockholm, Sweden;Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, Dept Genet & Genom Sci, New York, NY 10029 USA;Univ Tartu, Biomeedikum, Inst Biomedicine & Translat Med, Dept Pathophysiol, Tartu, Estonia;Karolinska Univ Ssjukhuset, Dept Med, Integrated Cardio Metab Ctr, Huddinge, Sweden.
    Codoni, Veronica
    Sorbonne Univ, UPMC Univ Paris 06, Team Genom & Pathophysiol Cardiovasc Dis, INSERM,UMR S 1166, Paris, France;CAN Inst Cardiometab & Nutr, Paris, France.
    Civelek, Mete
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA USA;Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA.
    Smith, Nicholas L.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA;VA Off Res & Dev, Seattle Epidemiol Res & Informat Ctr, Seattle, WA USA.
    Tregouet, David A.
    Sorbonne Univ, UPMC Univ Paris 06, Team Genom & Pathophysiol Cardiovasc Dis, INSERM,UMR S 1166, Paris, France;CAN Inst Cardiometab & Nutr, Paris, France.
    Christophersen, Ingrid E.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MGH, Cardiovasc Res Ctr, Boston, MA USA;Vestre Viken Hosp Trust, Baerum Hosp, Dept Med Res, Gjettum, Norway.
    Roselli, Carolina
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA.
    Lubitz, Steven A.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MGH, Cardiovasc Res Ctr, Boston, MA USA.
    Ellinor, Patrick T.
    Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA;MIT, 77 Massachusetts Ave, Cambridge, MA 02139 USA;MGH, Cardiovasc Res Ctr, Boston, MA USA.
    Tai, E. Shyong
    Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore;Natl Univ Hlth Syst, Singapore, Singapore.
    Kooner, Jaspal S.
    Imperial Coll London, Natl Heart & Lung Inst, London, England.
    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.
    van der Harst, Pim
    Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands.
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, London, England;Imperial Coll London, NIHR Imperial Biomed Res Ctr, London, England.
    Chambers, John C.
    Imperial Coll London, Dept Epidemiol & Biostat, London, England;Ealing Hosp NHS Trust, Dept Cardiol, Southall, Middx, England.
    Takeuchi, Fumihiko
    Natl Ctr Global Hlth & Med, Res Inst, Dept Gene Diagnost & Therapeut, Tokyo, Japan.
    Johnson, Andrew D.
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA;Natl Heart Lung & Blood Res Inst, Div Intramural Res, Populat Sci Branch, Framingham, MA USA.
    Sanghera, Dharambir K.
    Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat, Oklahoma City, OK 73190 USA;Univ Oklahoma, Hlth Sci Ctr, Coll Pharm, Dept Pharmaceut Sci, Oklahoma City, OK 73190 USA;Oklahoma Ctr Neurosci, Oklahoma City, OK USA.
    Melander, Olle
    Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Jern, Christina
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Pathol & Genet, Gothenburg, Sweden.
    Strbian, Daniel
    Helsinki Univ Hosp, Dept Neurol, Helsinki, Finland;Univ Helsinki, Clin Neurosci, Neurol, Helsinki, Finland.
    Fernandez-Cadenas, Israel
    Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Neurol Dept, Barcelona, Spain;Univ Autonoma Barcelona, Vall Hebron Hosp, Vall Hebron Inst Res, Neurovasc Res Lab,Med Dept, Barcelona, Spain;Fundacio Docencia & Recerca MutuaTerrassa, Stroke Pharmacogen & Genet, Recerca MutuaTerrassa, Terrassa, Spain.
    Longstreth, W. T., Jr.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA;Univ Washington, Dept Neurol, Seattle, WA 98195 USA.
    Rolfs, Arndt
    Univ Clin Rostock, Albrecht Kossel Inst, Rostock, Germany.
    Hata, Jun
    Kyushu Univ, Grad Sch Med Sci, Dept Epidemiol & Publ Hlth, Fukuoka, Japan.
    Woo, Daniel
    Univ Cincinnati, Coll Med, Cincinnati, OH USA.
    Rosand, Jonathan
    MGH, Ctr Genom Med, Boston, MA USA;MGH, J Philip Kistler Stroke Res Ctr, Dept Neurol, Boston, MA USA;Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
    Pare, Guillaume
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Hopewell, Jemma C.
    Univ Oxford, Nuffield Dept Populat Hlth, Clin Trial Serv Unit, Oxford, England;Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Saleheen, Danish
    Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
    Stefansson, Kari
    DeCODE Genet AMGEN Inc, Reykjavik, Iceland;Univ Iceland, Fac Med, Reykjavik, Iceland.
    Worrall, Bradford B.
    Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA;Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
    Kittner, Steven J.
    Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA;Baltimore VAMC, Baltimore, MD USA.
    Seshadri, Sudha
    Framingham Heart Dis Epidemiol Study, Framingham, MA USA;Univ Texas Hlth Sci Ctr San Antonio, Glenn Biggs Inst Alzheimers & Neurodegenerat Dis, San Antonio, TX 78229 USA.
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med, Houston, TX 77030 USA;Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX 77030 USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Markus, Hugh S.
    Univ Cambridge, Div Clin Neurosci, Stroke Res Grp, Cambridge, England.
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge, England.
    Kamatani, Yoichiro
    RIKEN Ctr Integrat Med Sci, Lab Stat Anal, Yokohama, Kanagawa, Japan;Kyoto Univ, Grad Sch Med, Ctr Genom Med, Kyoto, Japan.
    Debette, Stephanie
    Univ Bordeaux, Bordeaux Populat Hlth Res Ctr, INSERM, U1219, Bordeaux, France;Bordeaux Univ Hosp, Inst Neurodegenerat Dis, Dept Neurol, Bordeaux, France.
    Dichgans, Martin
    Univ Hosp, LMU Munich, Inst Stroke & Dementia Res ISD, Munich, Germany;Munich Cluster Syst Neurol SyNergy, Munich, Germany;German Ctr Neurodegenerat Dis DZNE, Munich, Germany.
    Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes2018In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 50, no 4, p. 524-537Article in journal (Refereed)
    Abstract [en]

    Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke sub-types. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.

  • 181. Malki, Ninoa
    et al.
    Koupil, Ilona
    Eloranta, Sandra
    Weibull, Caroline E.
    Tiikkaja, Sanna
    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.
    Sparen, Par
    Temporal Trends in Incidence of Myocardial Infarction and Ischemic Stroke by Socioeconomic Position in Sweden 1987-20102014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 8, p. e105279-Article in journal (Refereed)
    Abstract [en]

    Background: We analyzed temporal trends in the incidence of myocardial infarction and ischemic stroke in Sweden by socioeconomic position and investigated whether social inequalities in incidence of these diseases changed over time. Materials and Methods: We studied a cohort of almost three million Swedish residents born between 1932 and 1960 followed from 1987 until 2010. Incident cases of myocardial infarction and ischemic stroke were identified in the Swedish National Inpatient Register and Cause of Death Register. Socioeconomic position was retrieved from the Population and Housing Censuses. Incidence rates of myocardial infarction and ischemic stroke and incidence rate ratios comparing levels of socioeconomic position were estimated using flexible parametric survival models adjusted for calendar year, attained age, sex, and birth country. Results: The overall incidences of myocardial infarction and ischemic stroke decreased over time among men, but were stable over time among women. With regard to ischemic stroke incidence, socioeconomic inequality increased over time in the age group 55 to 59: the incidence rate ratios for low manual compared to high non-manual increased from 1.3 (95% CI: 1.2-1.4) in 1997 to 1.5 (1.4-1.7) in 2010 among men, and from 1.4 (1.3-1.6) in 1997 to 2.1 (1.8-2.5) in 2010 among women. The socioeconomic inequality in incidence of myocardial infarction was stable over time for both men and women. Conclusion: There was a decrease in myocardial infarction and ischemic stroke incidence over time among men but no significant change for women. Our study highlights existing, and in some cases increasing, social inequalities in the incidence of cardiovascular diseases.

  • 182.
    Marklund, Matti
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Univ New South Wales, George Inst Global Hlth, Sydney, NSW 2042, Australia.
    Morris, Andrew P.
    Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England.
    Mahajan, Anubha
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
    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;Stanford Univ, Stanford Cardiovasc Inst, Stanford, CA 94305 USA;Stanford Univ, Stanford Diabet Res Ctr, Stanford, CA 94305 USA.
    Lindgren, Cecilia M.
    Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England;Univ Oxford, Big Data Inst, Ka Shing Ctr Hlth Informat & Discovery, Oxford OX3 7LF, England.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Genome-Wide Association Studies of Estimated Fatty Acid Desaturase Activity in Serum and Adipose Tissue in Elderly Individuals: Associations with Insulin Sensitivity2018In: Nutrients, ISSN 2072-6643, E-ISSN 2072-6643, Vol. 10, no 11, article id 1791Article in journal (Refereed)
    Abstract [en]

    Fatty acid desaturases (FADS) catalyze the formation of unsaturated fatty acids and have been related to insulin sensitivity (IS). FADS activities differ between tissues and are influenced by genetic factors that may impact the link to IS. Genome-wide association studies of delta-5-desaturase (D5D), delta-6-desaturase (D6D) and stearoyl-CoA desaturase-1 (SCD) activities (estimated by product-to-precursor ratios of fatty acids analyzed by gas chromatography) in serum cholesterol esters (n = 1453) and adipose tissue (n = 783, all men) were performed in two Swedish population-based cohorts. Genome-wide significant associated loci were evaluated for associations with IS measured with a hyperinsulinemic euglycemic clamp (n = 554). Variants at the FADS1 were strongly associated with D5D in both cholesterol esters (p = 1.9 x 10(-70)) and adipose tissue (p = 1.1 x 10(-27)). Variants in three further loci were associated with D6D in cholesterol esters (FADS2, p = 3.0 x 10(-67); PDXDCI, p = 4.8 x 10(-8); and near MC4R, p = 3.7 x 10(-8)) but no associations with D6D in adipose tissue attained genome-wide significance. One locus was associated with SCD in adipose tissue (PKDL1, p = 2.2 x 10(-19)). Genetic variants near MC4R were associated with IS (p = 3.8 x 10(-3)). The FADS cluster was the main genetic determinant of estimated FADS activity. However, fatty acid (FA) ratios in adipose tissue and cholesterol esters represent FADS activities in separate tissues and are thus influenced by different genetic factors with potential varying effects on IS.

  • 183.
    Marouli, Eirini
    et al.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England;Queen Mary Univ London, Ctr Genom Hlth, Life Sci, London EC1M 6BQ, England.
    Del Greco, M. Fabiola
    Univ Lubeck, Inst Biomed, Eurac Res, Affiliated Inst, I-39100 Bolzano, Italy.
    Astley, Christina M.
    Boston Childrens Hosp, Boston, MA 02115 USA;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Yang, Jian
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia;Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
    Ahmad, Shafqat
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA;Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02215 USA.
    Berndt, Sonja, I
    NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
    Caulfield, Mark J.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England;Queen Mary Univ London, Barts Cardiovasc Biomed Res Ctr, Natl Inst Hlth Res, London EC1M 6BQ, England.
    Evangelou, Evangelos
    Imperial Coll London, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England;Univ Ioannina, Dept Hyg & Epidemiol, Med Sch, Ioannina 45110, Greece.
    McKnight, Barbara
    Univ Washington, Dept Biostat, Seattle, WA 98101 USA.
    Medina-Gomez, Carolina
    Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.
    van Vliet-Ostaptchouk, Jana V.
    Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, NL-9713 GZ Groningen, Netherlands.
    Warren, Helen R.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England;Queen Mary Univ London, Barts Cardiovasc Biomed Res Ctr, Natl Inst Hlth Res, London EC1M 6BQ, England.
    Zhu, Zhihong
    Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia.
    Hirschhorn, Joel N.
    Boston Childrens Hosp, Boston, MA 02115 USA;Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
    Kutalik, Zoltan
    Lausanne Univ Hosp, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.
    Deloukas, Panos
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England;Queen Mary Univ London, Ctr Genom Hlth, Life Sci, London EC1M 6BQ, England;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia.
    Mendelian randomisation analyses find pulmonary factors mediate the effect of height on coronary artery disease2019In: COMMUNICATIONS BIOLOGY, ISSN 2399-3642, Vol. 2, article id 119Article in journal (Refereed)
    Abstract [en]

    There is evidence that lower height is associated with a higher risk of coronary artery disease (CAD) and increased risk of type 2 diabetes (T2D). It is not clear though whether these associations are causal, direct or mediated by other factors. Here we show that one standard deviation higher genetically determined height (similar to 6.5 cm) is causally associated with a 16% decrease in CAD risk (OR = 0.84, 95% CI 0.80-0.87). This causal association remains after performing sensitivity analyses relaxing pleiotropy assumptions. The causal effect of height on CAD risk is reduced by 1-3% after adjustment for potential mediators (lipids, blood pressure, glycaemic traits, body mass index, socio-economic status). In contrast, our data suggest that lung function (measured by forced expiratory volume [FEV1] and forced vital capacity [FVC]) is a mediator of the effect of height on CAD. We observe no direct causal effect of height on the risk of T2D.

  • 184.
    Marouli, Eirini
    et al.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
    Graff, Mariaelisa
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Medina-Gomez, Carolina
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Lo, Ken Sin
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Wood, Andrew R.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Kjaer, Troels R.
    Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus, Denmark..
    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..
    Lu, Yingchang
    Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37203 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 10069 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 10069 USA..
    Highland, Heather M.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA.;Univ Texas Hlth Sci Ctr Houston, Univ Texas Grad Sch Biomed Sci Houston, Univ Texas Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Rueger, Sina
    Univ Lausanne Hosp, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland..
    Thorleifsson, Gudmar
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland..
    Justice, Anne E.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Lamparter, David
    Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Lausanne, Dept Comp Biol, CH-1011 Lausanne, Switzerland..
    Stirrups, Kathleen E.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Univ Cambridge, Dept Hematol, Cambridge CB2 0PT, England..
    Turcot, Valerie
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Young, Kristin L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Winkler, Thomas W.
    Univ Regensburg, Dept Genet Epidemiol, D-93051 Regensburg, Germany..
    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, EE-51010 Tartu, Estonia..
    Karaderi, Tugce
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    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 63108 USA..
    Masca, Nicholas G. D.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Ng, Maggie C. Y.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA..
    Mudgal, Poorva
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA..
    Rivas, Manuel A.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Nuffield Dept Clin Med, Oxford OX3 7BN, England..
    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..
    Mahajan, Anubha
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Guo, Xiuqing
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Abecasis, Goncalo
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Aben, Katja K.
    Netherland Comprehens Canc Org, NL-3501 DB Utrecht, Netherlands.;Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Adair, Linda S.
    Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA..
    Alam, Dewan S.
    Ctr Control Chron Dis, Dhaka 1212, Bangladesh..
    Albrecht, Eva
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany..
    Allin, Kristine H.
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Allison, Matthew
    Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA..
    Amouyel, Philippe
    INSERM, U1167, F-59019 Lille, France.;Inst Pasteur, U1167, F-59019 Lille, France.;Univ Lille, U1167, RID AGE Risk Factors & Mol Determinants Aging Rel, F-59019 Lille, France..
    Appel, Emil V.
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Arveiler, Dominique
    Univ Strasbourg, Dept Epidemiol & Publ Hlth, F-67085 Strasbourg, France.;Univ Hosp Strasbourg, Dept Publ Hlth, F-67081 Strasbourg, France..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands.;ICIN Netherland 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
    INSERM, Ctr Rech Epidemiol & Sante Populat CESP, U1018, Villejuif, France..
    Banas, Bernhard
    Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany..
    Bang, Lia E.
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, DK-2100 Copenhagen, Denmark..
    Benn, Marianne
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Bergmann, Sven
    Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland.;Univ Lausanne, Dept Comp Biol, CH-1011 Lausanne, Switzerland..
    Bielak, Lawrence F.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Blueher, Matthias
    Univ Leipzig, Dept Med, D-04103 Leipzig, Germany..
    Boeing, Heiner
    German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Epidemiol, D-14558 Nuthetal, Germany..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Boeger, Carsten A.
    Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany..
    Bonnycastle, Lori L.
    NHGRI, Med Genom & Metabol Genet Branch, NIH, Bethesda, MD 20892 USA..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 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 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Dept Biochem, Winston Salem, NC 27157 USA..
    Brandslund, Ivan
    Lillebaelt Hosp, Dept Clin Biochem, DK-7100 Vejle, Denmark.;Univ Southern Denmark, Inst Reg Hlth Res, DK-5000 Odense, Denmark..
    Breen, Gerome
    Kings Coll London, Inst Psychiat Psychol & Neurosci, MRC Social Genet & Dev Psychiat Ctr, London SE5 8AF, England.;NIHR Biomed Res Ctr Mental Hlth Maudsley, London SE5 8AF, England..
    Brilliant, Murray H.
    Marshfield Clin Res Fdn, Marshfield, WI 54449 USA..
    Broer, Linda
    Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Burt, Amber A.
    Univ Washington, Dept Med, Seattle, WA 98195 USA..
    Butterworth, Adam S.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England..
    Carey, David J.
    Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA..
    Caulfield, Mark J.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England..
    Chambers, John C.
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Middlesex UB1 3HW, England.;Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.;Univ London Imperial Coll Sci Technol & Med, Healthcare NHS Trust, London W12 0HS, England..
    Chasman, Daniel I.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA..
    Chen, Yii-Der Ida
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Chowdhury, Rajiv
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England..
    Christensen, Cramer
    Lillebaelt Hosp, Dept Med, DK-7100 Vejle, Denmark..
    Chu, Audrey Y.
    Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA.;NHLBI, Framingham Heart Study, Framingham, MA 01702 USA..
    Cocca, Massimiliano
    Univ Trieste, Dept Med Surg & Hlth Sci, I-34100 Trieste, Italy..
    Collins, Francis S.
    NHGRI, Med Genom & Metabol Genet Branch, NIH, Bethesda, MD 20892 USA..
    Cook, James P.
    Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England..
    Corley, Janie
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Galbany, Jordi Corominas
    Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands..
    Cox, Amanda J.
    Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC 27157 USA.;Griffith Univ, Menzies Hlth Inst Queensland, Southport, Qld, Australia..
    Cuellar-Partida, Gabriel
    Univ Queensland, Diamantina Inst, Brisbane, Qld 4072, Australia.;QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Danesh, John
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England.;Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England.;Univ Cambridge, Dept Med, Cambridge Escellence, British Heart Fdn, Cambridge CB2 0QQ, England..
    Davies, Gail
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    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 Genet, NL-3584 CX Utrecht, Netherlands..
    de Borst, Gert J.
    Univ Med Ctr Utrecht, Dept Vasc Surg, Div Surg Specialties, NL-3584 CX Utrecht, Netherlands..
    de Denus, Simon
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada..
    de Groot, Mark C. H.
    Univ Med Ctr Utrecht, Div Lab & Pharm, Dept Clin Chem & Haematol, NL-3508 GA Utrecht, Netherlands.;Univ Utrecht, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht Inst Pharmaceut Sci, NL-3508 TB Utrecht, Netherlands..
    de Mutsert, Renee
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Dedoussis, George
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens 17671, Greece..
    Demerath, Ellen W.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA..
    den Hollander, Anneke I.
    Radbound Univ Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands..
    Dennis, Joe G.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Di Angelantonio, Emanuele
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Cambridge, NIHR Blood & Transplant Res Unit Donor Hlth Genom, Cambridge CB1 8RN, England..
    Drenos, Fotios
    UCL, Inst Cardiovasc Sci, London WC1E 6JF, England.;Univ Bristol, Sch Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Du, Mengmeng
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.;Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10017 USA..
    Dunning, Alison M.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.;Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland..
    Easton, Douglas F.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.;Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Ebeling, Tapani
    Oulu Univ Hosp, Dept Med, Oulu 90029, Finland.;Univ Oulu, Res Unit Internal Med, FI-90014 Oulu, Finland..
    Edwards, Todd L.
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Med,Div Epidemiol, Nashville, TN 37203 USA..
    Ellinor, Patrick T.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA..
    Elliott, Paul
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Evangelou, Evangelos
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece..
    Farmaki, Aliki-Eleni
    Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens 17671, Greece..
    Faul, Jessica D.
    Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI 48104 USA..
    Feitosa, Mary F.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA..
    Feng, Shuang
    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..
    Ferrario, Marco M.
    Univ Insubria, Dept Clin & Expt Med, Res Ctr Epidemiol & Prevent Med, I-21100 Varese, Italy..
    Ferrieres, Jean
    Toulouse Univ, Sch Med, F-31059 Toulouse, France..
    Florez, Jose C.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA..
    Ford, Ian
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Franks, Paul W.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden.;Harvard Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.;Umea Univ, Med Unit, Dept Publ Hlth & Clin Med, S-90187 Umea, Sweden..
    Frikke-Schmidt, Ruth
    Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark..
    Galesloot, Tessel E.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Gan, Wei
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Gandin, Ilaria
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy..
    Gasparini, Paolo
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy.;Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar..
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Giri, Ayush
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Med,Div Epidemiol, Nashville, TN 37203 USA..
    Girotto, Giorgia
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy.;Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar..
    Gordon, Scott D.
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Gordon-Larsen, Penny
    Univ N Carolina, Caroline Populat Ctr, Chapel Hill, NC 27514 USA.;Univ N Carolina, Dept Nutr, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27514 USA..
    Gorski, Mathias
    Univ Regensburg, Dept Genet Epidemiol, D-93051 Regensburg, Germany.;Univ Hosp Regensburg, Dept Nephrol, D-93042 Regensburg, Germany.;Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany..
    Grarup, Niels
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Gudnason, Vilmundur
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;Icelandic Heart Assoc, IS-201 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.
    Hansen, Torben
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Harris, Kathleen Mullan
    Univ N Carolina, Caroline Populat Ctr, Chapel Hill, NC 27514 USA.;Univ N Carolina, Dept Sociol, Chapel Hill, NC 27514 USA..
    Harris, Tamara B.
    NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Hattersley, Andrew T.
    Univ Exeter, Univ Exeter Med Sch, Exeter EX2 5DW, Devon, England..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRCHGU, Edinburgh EH4 2XU, Midlothian, Scotland..
    He, Liang
    Duke Univ, Social Sci Res Inst, Biodemog Aging Res Unit, Durham, NC 27708 USA.;Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland..
    Heid, Iris M.
    Univ Regensburg, Dept Genet Epidemiol, D-93051 Regensburg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany..
    Heikkila, Kauko
    Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland..
    Helgeland, Oyvind
    Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebson Ctr Diabet Res, N-5020 Bergen, Norway..
    Hernesniemi, Jussi
    Tampere Univ Hosp, Dept Cardiol, Ctr Heart, FI-33521 Tampere, Finland.;Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Hewitt, Alex W.
    Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic 3002, Australia.;Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Vis Sci, Perth, WA 6009, Australia.;Univ Tasmania, Menzies Res Inst Tasmania, Hobart, Tas 7000, Australia..
    Hocking, Lynne J.
    Univ Edinburgh, Ctr Genom & Expt Med, Generat Scotland, Edinburgh EH4 2XU, Midlothian, Scotland.;Univ Aberdeen, Div Appl Med, Musculoskeletal Res Programme, Aberdeen AB25 2ZD, Scotland..
    Hollensted, Mette
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Holmen, Oddgeir L.
    Norwegian Univ Sci & Technol, NTNU, Dept Publ Hlth, KG Jebsen Ctr Genet Epidemiol, N-7600 Trondheim, Norway..
    Hovingh, G. Kees
    AMC, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands..
    Howson, Joanna M. M.
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England..
    Hoyng, Carel B.
    Radbound Univ Med Ctr, Dept Ophthalmol, NL-6500 HB Nijmegen, Netherlands..
    Huang, Paul L.
    Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Hveem, Kristian
    Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, N-7600 Levanger, Norway..
    Ikram, M. Arfan
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Neurol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Radiol, NL-3015 GE Rotterdam, Netherlands..
    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.
    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, SE-90185 Umea, Sweden.;Res Unit Skelleftea, SE-93141 Skelleftea, Sweden..
    Jarvik, Gail P.
    Univ Washington, Dept Med, Seattle, WA 98195 USA.;Univ Washington, Dept Genom Sci, Seattle, WA 98195 USA..
    Jensen, Gorm B.
    Frederiksberg Univ Hosp, Copenhagen City Heart Study, DK-2000 Frederiksberg, Denmark..
    Jhun, Min A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Jia, Yucheng
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Jiang, Xuejuan
    Univ Calif Los Angeles, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.;Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90089 USA..
    Johansson, Stefan
    Univ Bergen, Dept Clin Sci, KG Jebson Ctr Diabet Res, N-5020 Bergen, Norway.;Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway..
    Jorgensen, Marit E.
    Univ Southern Denmark, Natl Inst Publ Hlth, DK-1353 Copenhagen, Denmark.;Steno Diabet Ctr, DK-2820 Gentofte, Denmark..
    Jorgensen, Torben
    Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Aalborg Hosp, DK-9000 Aalborg, Denmark.;Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark..
    Jousilahti, Pekka
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Jukema, J. Wouter
    Leiden Univ Med Ctr, Dept Cardiol, NL-2333 Leiden, Netherlands.;Interuniv Cardiol Inst Netherlands, NL-2333 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..
    Kahn, Rene S.
    Ctr Med Univ Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CG Utrecht, Netherlands..
    Kahonen, Mika
    Univ Tampere, Sch Med, Dept Clin Physiol, Tampere 33014, Finland..
    Kamstrup, Pia R.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark..
    Kanoni, Stavroula
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
    Kaprio, Jaakko
    Univ Helsinki, Dept Publ Hlth, FI-00014 Helsinki, Finland.;Univ Helsinki, Inst Mol Med Finland FIMM, FI-00014 Helsinki, Finland.;Natl Inst Hlth & Welf, FI-00271 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 Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Kee, Frank
    Queens Univ Belfast, UKCRC Ctr Excellence Publ Hlth Res, Belfast BT12 6BJ, Antrim, North Ireland..
    Keeman, Renske
    Netherlands Canc Inst, Antoni van Leewenhoek Hosp, NL-1066 CX Amsterdam, Netherlands..
    Kiemeney, Lambertus A.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Kitajima, Hidetoshi
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England..
    Kluivers, Kirsten B.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Kocher, Thomas
    Univ Med Greifswald, Dept Restorat Dent Periodontol & Endodontol, D-17475 Greifswald, Germany..
    Komulainen, Pirjo
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland..
    Kontto, Jukka
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Kooner, Jaspal S.
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Middlesex UB1 3HW, England.;Univ London Imperial Coll Sci Technol & Med, Healthcare NHS Trust, London W12 0HS, England.;Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Hammersmith Hosp Campus, London W12 0NN, England..
    Kooperberg, Charles
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Kovacs, Peter
    Univ Leipzig, IFB Adipos Dis, D-04103 Leipzig, Germany..
    Kriebel, Jennifer
    German Ctr Diabet Res, D-85764 Munich, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, D-85764 Neuherberg, Germany.;Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, D-85764 Neuherberg, Germany..
    Kuivaniemi, Helena
    Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Dept Psychiat, ZA-7505 Tygerberg, Western Cape, South Africa.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Div Mol Biol & Human Genet, ZA-7505 Tygerberg, Western Cape, South Africa..
    Kury, Sebastien
    CHU Nantes, Serv Genet Med, F-44093 Nantes, France..
    Kuusisto, Johanna
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, SF-70210 Kuopio, Finland..
    La Bianca, Martina
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy..
    Laakso, Markku
    Univ Eastern Finland, Inst Clin Med, Internal Med, Kuopio 70210, Finland.;Kuopio Univ Hosp, SF-70210 Kuopio, Finland..
    Lakka, Timo A.
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland.;Univ Eastern Finland, Inst Biomed & Physiol, Kuopio 70210, Finland..
    Lange, Ethan M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Lange, Leslie A.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Langefeld, Carl D.
    Wake Forest Sch Med, Dept Biostat Sci, Winston Salem, NC 27157 USA.;Wake Forest Sch Med, Ctr Publ Hlth Genom, Winston Salem, NC 27157 USA..
    Langenberg, Claudia
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Larson, Eric B.
    Univ Washington, Dept Med, Seattle, WA 98195 USA.;Grp Hlth Res Inst, Seattle, WA 98101 USA.;Univ Washington, Dept Hlth Serv, Seattle, WA 98101 USA..
    Lee, I-Te
    Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrinol & Metab, Taichung 407, Taiwan.;Natl Yang Ming Univ, Sch Med, Taipei 112, Taiwan.;Chung Shan Med Univ, Sch Med, Taichung 402, Taiwan..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Lewis, Cora E.
    Univ Alabama Birmingham, Div Prevent Med, Birmingham, AL 35205 USA..
    Li, Huaixing
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Li, Jin
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Palo Alto, CA 94305 USA..
    Li-Gao, Ruifang
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands..
    Lin, Honghuang
    Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA..
    Lin, Li-An
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Lin, Xu
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, 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, FI-00271 Helsinki, Finland..
    Linneberg, Allan
    Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark.;Rigshosp, Dept Expt Med, DK-2200 Copenhagen, Denmark..
    Liu, Yeheng
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Liu, Yongmei
    Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC 27157 USA..
    Lophatananon, Artitaya
    Warsaw Acad Med & Hosp, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England..
    Luan, Jian'an
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Lubitz, Steven A.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Mackey, David A.
    Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Vis Sci, Perth, WA 6009, Australia..
    Madden, Pamela A. F.
    Washington Univ, Dept Psychiat, St Louis, MO 63110 USA..
    Manning, Alisa K.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland..
    Mannisto, Satu
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Marenne, Gaelle
    Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Marten, Jonathan
    Univ Edinburgh, Inst Genet & Mol Med, MRCHGU, Edinburgh EH4 2XU, Midlothian, Scotland..
    Martin, Nicholas G.
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Mazul, Angela L.
    Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Meidtner, Karina
    German Ctr Diabet Res, D-85764 Munich, Germany.;German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, D-14558 Nuthetal, Germany..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Mitchell, Paul
    Univ Sydney, Ctr Vis Res, Westmead Millennium Inst Med Res, Sydney, NSW 2022, Australia.;Univ Sydney, Dept Ophthalmol, Sydney, NSW 2022, Australia..
    Mohlke, Karen L.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Mook-Kanamori, Dennis O.
    Leiden Univ, Med Ctr, Dept Clin Epidemiol, NL-2300 RC Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, NL-2300 RC Leiden, Netherlands..
    Morgan, Anna
    Univ Trieste, Dept Med Sci, I-34137 Trieste, Italy..
    Morris, Andrew D.
    Univ Edinburgh, Ctr Global Hlth Res, Ushar Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Morris, Andrew P.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Liverpool, Dept Biostat, Liverpool L69 3GL, Merseyside, England..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Genet Epidemiol, D-85764 Neuherberg, Germany.;Univ Munich, Dept Med 1, D-81377 Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, D-80802 Munich, Germany..
    Munroe, Patricia B.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England..
    Nalls, Mike A.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Nauck, Matthias
    DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, D-17475 Greifswald, Germany.;Univ Med Greifswald, Inst Clin Chem, D-17475 Greifswald, Germany.;Univ Med Greifswald, Lab Med, D-17475 Greifswald, Germany..
    Nelson, Christopher P.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Neville, Matt
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Nielsen, Sune F.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Nikus, Kjell
    Univ Tampere, Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere 33521, Finland.;Univ Tampere, Sch Med, Tampere 33521, Finland..
    Njolstad, Pal R.
    Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway.;Univ Bergen, Dept Clin Sci, KG Jebson Ctr Diabet Res, N-5020 Bergen, Norway..
    Nordestgaard, Borge G.
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Ntalla, Ioanna
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England..
    O'Connel, Jeffrey R.
    Univ Maryland, Sch Med, Dept Med, Program Personalized Med, Baltimore, MD 21201 USA..
    Oksa, Heikki
    Tampere Univ Hosp, Dept Med, Tampere 33521, Finland..
    Loohuis, Loes M. Olde
    Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA..
    Ophoff, Roel A.
    Ctr Med Univ Utrecht, Brain Ctr Rudolf Magnus, Dept Psychiat, NL-3584 CG Utrecht, Netherlands.;Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA..
    Owen, Katharine R.
    Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    Packard, Chris J.
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Padmanabhan, Sandosh
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Palmer, Colin N. A.
    Ninewells Hosp & Med Sch, Med Res Inst, Pat Macpherson Ctr Pharmacogenet & Pharmacogenom, Dundee DD1 9SY, Scotland..
    Pasterkamp, Gerard
    Univ Med Ctr Utrecht, Div Labs & Pharm, Lab Clin Chem & Hematol, NL-3584 CX Utrecht, Netherlands..
    Patel, Aniruddh P.
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA..
    Pattie, Alison
    Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Pedersen, Oluf
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Peissig, Peggy L.
    Marshfield Clin Res Fdn, Marshfield, WI 54449 USA..
    Peloso, Gina M.
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Broad Inst, Med & Populat Genet Program, Cambridge, MA 02141 USA..
    Pennell, Craig E.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia..
    Perola, Markus
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland.;Univ Helsinki, Inst Mol Med FIMM, FI-00014 Helsinki, Finland.;Univ Helsinki, Diabet & Obes Res Program, FI-00014 Helsinki, Finland.;Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Perry, James A.
    Univ Maryland, Sch Med, Dept Med, Program Personalized Med, Baltimore, MD 21201 USA..
    Perry, John R. B.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Person, Thomas N.
    Marshfield Clin Res Fdn, Marshfield, WI 54449 USA..
    Pirie, Ailith
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Polasek, Ozren
    Univ Edinburgh, Ctr Global Hlth Res, Ushar Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland.;Univ Split, Sch Med, Split 21000, Croatia..
    Posthuma, Danielle
    Vrije Univ Amsterdam, Dept Complex Trait Genet, Ctr Neurogenom & Cognit Res, NL-1081 HV Amsterdam, Netherlands.;Vrije Univ Amsterdam Med Ctr, Dept Clin Genet, Neurosci Campus Amsterdam, NL-1081 HV Amsterdam, Netherlands..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FIN-20520 Turku, Finland..
    Rasheed, Asif
    Ctr Noncommunicable Dis, Karachi, Pakistan..
    Rauramaa, Rainer
    Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio 70100, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland..
    Reilly, Dermot F.
    MRL Merck & Co Inc, Genet & Pharmacogenom, Boston, MA 02115 USA..
    Reiner, Alex P.
    Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.;Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA..
    Renstrom, Frida
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden.;Umea Univ, Dept Biobank Res, SE-90187 Umea, Sweden..
    Ridker, Paul M.
    Harvard Med Sch, Boston, MA 02115 USA.;Brigham & Womens & Harvard Med Sch, Div Prevent Med, Boston, MA 02115 USA.;Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA..
    Rioux, John D.
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada..
    Robertson, Neil
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England..
    Robino, Antonietta
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy..
    Rolandsson, Olov
    Umea Univ, Dept Publ Hlth & Clin Med, SE-90185 Umea, Sweden.;Umea Univ, Unit Family Med, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden..
    Rudan, Igor
    Univ Edinburgh, Ctr Global Hlth Res, Ushar Inst Populat Hlth Sci & Informat, Edinburgh EH8 9AG, Midlothian, Scotland..
    Ruth, Katherine S.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Saleheen, Danish
    Ctr Noncommunicable Dis, Karachi, Pakistan.;Univ Penn, Perelman Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA..
    Salomaa, Veikko
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland..
    Samani, Nilesh J.
    Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.;Glenfield Hosp, NIHR Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England..
    Sandow, Kevin
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Sapkota, Yadav
    QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia..
    Sattar, Naveed
    Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Schmidt, Marjanka K.
    Netherlands Canc Inst, Antoni van Leewenhoek Hosp, NL-1066 CX Amsterdam, Netherlands..
    Schreiner, Pamela J.
    Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55454 USA..
    Schulze, Matthias B.
    German Ctr Diabet Res, D-85764 Munich, Germany.;German Inst Human Nutr Potsdam Rehbruecke DIfE, Dept Mol Epidemiol, D-14558 Nuthetal, Germany..
    Scott, Robert A.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Segura-Lepe, Marcelo P.
    Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Shah, Svati
    Duke Univ, Durham, NC 27703 USA..
    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..
    Sivapalaratnam, Suthesh
    Massachusetts Gen Hosp, Boston, MA 02114 USA.;Univ Cambridge, Dept Haematol, Cambridge CB2 0PT, England.;AMC, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands..
    Small, Kerrin S.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England..
    Smith, Albert Vernon
    Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;Icelandic Heart Assoc, IS-201 Kopavogur, Iceland..
    Smith, Jennifer A.
    Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA..
    Southam, Lorraine
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Spector, Timothy D.
    Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, 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 EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Steinthorsdottir, Valgerdur
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland..
    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, D-04103 Leipzig, Germany.;Univ Leipzig, Dept Med, D-04103 Leipzig, Germany..
    Surendran, Praveen
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England..
    't Hart, Leen M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands.;Leiden Univ, Med Ctr, Dept Mol & Cell Biol, NL-2333 ZC Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Mol Epidemiol, NL-2333 ZC Leiden, Netherlands..
    Tansey, Katherine E.
    Cardiff Univ, Coll Biomed & Life Sci, Cardiff CF14 4EP, S Glam, Wales.;Univ Bristol, Dept Social & Community Med, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England..
    Tardif, Jean-Claude
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada..
    Taylor, Kent D.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Teumer, Alexander
    Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.;Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany..
    Thompson, Deborah J.
    Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Thorsteinsdottir, Unnur
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Thuesen, Betina H.
    Capital Reg Denmark, Res Ctr Prevent & Hlth, DK-2600 Glostrup, Denmark..
    Toenjes, Anke
    Univ Leipzig, Dept Womens & Child Hlth, Ctr Pediat Res, D-04103 Leipzig, Germany..
    Tromp, Gerard
    Sigfried & Janet Weis Ctr Res, Danville, PA 17822 USA.;Univ Stellenbosch, Fac Med & Hlth Sci, Dept Biomed Sci, Div Human Genet & Mol Biol, ZA-7505 Tygerberg, Western Cape, South Africa..
    Trompet, Stella
    Leiden Univ Med Ctr, Dept Cardiol, NL-2333 Leiden, Netherlands.;Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2333 Leiden, Netherlands..
    Tsafantakis, Emmanouil
    Anogia Med Ctr, Anogia, Greece..
    Tuomilehto, Jaakko
    Natl Inst Hlth & Welf, FI-00271 Helsinki, Finland.;Danube Univ Krems, Ctr Vasc Prevent, A-3500 Krems, Austria.;Dasman Diabet Inst, Dasman 15462, Kuwait.;King Abdulaziz Univ, Diabet Res Grp, Jeddah 21589, Saudi Arabia..
    Tybjaerg-Hansen, Anne
    Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark.;Copenhagen Univ Hosp, Rigshosp, Dept Clin Biochem, DK-2100 Copenhagen, Denmark..
    Tyrer, Jonathan P.
    Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England..
    Uher, Rudolf
    Dalhousie Univ, Dept Psychiat, Halifax, NS B3H 4R2, Canada..
    Uitterlinden, Andre G.
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    Ulivi, Sheila
    Inst Maternal & Child Hlth IRCCS Burlo Garofolo, I-34137 Trieste, Italy..
    van der Laan, Sander W.
    Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, NL-3584 CX Utrecht, Netherlands..
    Van Der Leij, Andries R.
    Univ Amsterdam, Dept Brain & Cognit, NL-1018 WS Amsterdam, Netherlands..
    van Duijn, Cornelia M.
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands..
    van Schoor, Natasja M.
    Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands..
    van Setten, Jessica
    Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands..
    Varbo, Anette
    Copenhagen Univ Hosp, Herlev & Gentofte Hosp, Dept Clin Biochem, DK-2730 Herlev, Denmark.;Univ Copenhagen, Fac Med & Hlth Sci, DK-2200 Copenhagen, Denmark..
    Varga, Tibor V.
    Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, SE-20502 Malmo, Sweden..
    Varma, Rohit
    Univ Southern Calif, Keck Sch Med, Dept Ophthalmol, USC Roski Eye Inst, Los Angeles, CA 90089 USA..
    Edwards, Digna R. Velez
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Dept Obstet & Gynecol, Nashville, TN 37203 USA..
    Vermeulen, Sita H.
    Radboud Univ Nijmegen, Med Ctr, NL-6500 HB Nijmegen, Netherlands..
    Vestergaard, Henrik
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark..
    Vitart, Veronique
    Univ Edinburgh, Inst Genet & Mol Med, MRCHGU, Edinburgh EH4 2XU, Midlothian, Scotland..
    Vogt, Thomas F.
    MRL Merck Co Inc, Cardiometab Dis, Kenilworth, NJ 07033 USA..
    Vozzi, Diego
    Sidra Med & Res Ctr, Div Expt Genet, Doha 26999, Qatar..
    Walker, Mark
    Newcastle Univ, Sch Med, Inst Cellular Med, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England..
    Wang, Feijie
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Wang, Carol A.
    Univ Western Australia, Sch Womens & Infants Hlth, Perth, WA 6009, Australia..
    Wang, Shuai
    Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA..
    Wang, Yiqin
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Wareham, Nicholas J.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Warren, Helen R.
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;Queen Mary Univ, Barts & London Sch Med & Dent, NIHR Barts Cardiovasc Res Unit, London EC1M 6BQ, England..
    Wessel, Jennifer
    Indiana Univ, Fairbanks Sch Publ Hlth, Diabet Translat Res Ctr, Dept Epidemiol & Med, Indianapolis, IN 46202 USA.;Indiana Univ, Sch Med, Indianapolis, IN 46202 USA..
    Willems, Sara M.
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, England..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Witte, Daniel R.
    Danish Diabet Acad, DK-5000 Odense, Denmark.;Aarhus Univ, Dept Publ Hlth, DK-8000 Aarhus, Denmark..
    Woods, Michael O.
    Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF A1B 3V6, Canada..
    Wu, Ying
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Yaghootkar, Hanieh
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Yao, Jie
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Yao, Pang
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Yerges-Armstrong, Laura M.
    Univ Maryland, Sch Med, Dept Med, Program Personalized Med, Baltimore, MD 21201 USA.;GlaxoSmithKlein, King Of Prussia, PA 19406 USA..
    Young, Robin
    Univ Cambridge, Dept Publ Hlth & Primary Care, MRC BHF Cardiovasc Epidemiol Unit, Cambridge CB1 8RN, England.;Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland..
    Zeggini, Eleftheria
    Wellcome Trust Sanger Inst, Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Zhan, Xiaowei
    Univ Texas Southwestern Med Ctr Dallas, Quantitat Biomed Res Ctr, Ctr Genet Host Def, Dept Clin Sci, Dallas, TX 75390 USA..
    Zhang, Weihua
    London North West Healthcare NHS Trust, Ealing Hosp, Dept Cardiol, Middlesex UB1 3HW, England.;Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Zhao, Jing Hua
    Univ Cambridge, Sch Clin Med, Inst Metab Sci, MRC Epidemiol Unit, Cambridge CB2 0QQ, 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 19104 USA..
    Zheng, He
    Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci,Key Lab Nutr & Metab, Shanghai 200031, Peoples R China..
    Zhou, Wei
    Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.;Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA..
    Rotter, Jerome I.
    LABioMed Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA..
    Boehnke, Michael
    Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA.;Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA..
    Kathiresan, Sekar
    Broad Inst MIT & Harvard, Cambridge, MA 02142 USA.;Harvard Med Sch, Boston, MA 02115 USA.;Massachusetts Gen Hosp, Boston, MA 02114 USA..
    McCarthy, Mark I.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Radcliffe Dept Med, Oxford Ctr Diabetes Endocrinol & Metab, Oxford OX3 7LE, England.;Oxford Univ Hosp Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LE, England..
    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..
    Stefansson, Kari
    deCODE Genet Amgen Inc, IS-101 Reykjavik, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Borecki, Ingrid B.
    Washington Univ, Sch Med, Dept Genet, Div Stat Genom, St Louis, MO 63108 USA..
    Liu, Dajiang J.
    Penn State Univ, Coll Med, Inst Personalized Med, Dept Publ Hlth Sci, Hershey, PA 17033 USA..
    North, Kari E.
    Dept Epidemiol, Chapel Hill, NC 27514 USA.;Carolina Ctr Genome Sci, Chapel Hill, NC 27514 USA..
    Heard-Costa, Nancy L.
    NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.;Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA..
    Pers, Tune H.
    Univ Copenhagen, Fac Med & Hlth Sci, Novo Nordisk Fdn Ctr Basic Metab Res, DK-2100 Copenhagen, Denmark.;Statens Serum Inst, Dept Epidemiol Res, DK-2200 Copenhagen, Denmark..
    Lindgren, Cecilia M.
    Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Univ Oxford, Big Data Inst, Li Ka Shing Ctr Hlth Informat & Discovery, Oxford OX3 7BN, England..
    Oxvig, Claus
    Aarhus Univ, Dept Mol Biol & Genet, DK-8000 Aarhus, Denmark..
    Kutalik, Zoltan
    Univ Lausanne Hosp, Inst Social & Prevent Med, CH-1010 Lausanne, Switzerland.;Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland..
    Rivadeneira, Fernando
    Erasmus Sch Ctr, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;Erasmus Sch Ctr, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands..
    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 10069 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10069 USA..
    Frayling, Timothy M.
    Univ Exeter, Sch Med, Genet Complex Traits, Exeter EX2 5DW, Devon, England..
    Hirschhorn, Joel N.
    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.;Harvard Med Sch, Dept Pediat & Genet, Boston, MA 02115 USA..
    Deloukas, Panos
    Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, London EC1M 6BQ, England.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia..
    Lettre, Guillaume
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Med, Dept Med, Montreal, PQ H3T 1J4, Canada..
    Rare and low-frequency coding variants alter human adult height2017In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 542, no 7640, p. 186-190Article in journal (Refereed)
    Abstract [en]

    Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.

  • 185.
    Martinez Perez, Guillermo
    et al.
    Univ Zaragoza, Fac Hlth Sci, Dept Physiat & Nursing, E-50009 Zaragoza, Spain..
    Mubanga, Mwenya
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala Univ, Uppsala, Sweden..
    Tomas Aznar, Concepcion
    Univ Zaragoza, Fac Hlth Sci, Dept Physiat & Nursing, E-50009 Zaragoza, Spain..
    Bagnol, Brigitte
    Univ Witwatersrand, Dept Anthropol, ZA-2050 Johannesburg, South Africa..
    Zambian Women in South Africa: Insights Into Health Experiences of Labia Elongation2015In: Journal of Sex Research, ISSN 0022-4499, E-ISSN 1559-8519, Vol. 52, no 8, p. 857-867Article in journal (Refereed)
    Abstract [en]

    Labia minora elongation consists in the manual stretching of the inner lips of the external genitalia. This practice is documented in east and southern Africa. The experiences of African women in the diaspora practicing elongation are not thoroughly understood. The purpose of this qualitative study was to explore the health harms and benefits associated with this practice of Zambian women who have migrated to Cape Town, South Africa. Twenty women and seventeen men participated in this study. Between December 2013 and May 2014, in-depth interviews and natural group discussions were conducted with the participants. The focus of this article is to report on the emic of the women related to notions of health, hygiene, and well-being. Labial elongation is perceived as a practice involving minor, short-term adverse effects that can be prevented by following some basic hygiene. Overall, personal and social value is placed on this practice because of its reported benefits for the sexual health of men and women, and for women's femininity and self-image. Further research is necessary on how female genital modifications influence Zambians' sexual preferences to inform the development of culturally appropriate health promotion interventions.

  • 186.
    Megquier, Katherine
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Tonomura, Noriko
    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.
    Noh, Hyun Ji
    Broad Institute.
    Turner-Maier, Jason
    Broad Institute.
    Swofford, Ross
    Broad Institute.
    Koltookian, Michele
    Broad Institute.
    Biagi, Tara
    Fryc, Sarah
    Arendt, Maja Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Häggström, Jens
    Barber, Lisa
    Tufts Cummings School of Veterinary Medicine.
    Burgess, Kristine
    Tufts Cummings School of Veterinary Medicine.
    Thomas, Rachael
    NCSU.
    Breen, Matthew
    NCSU.
    Modiano, Jaime
    University of Minnesota.
    Elvers, Ingegerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Azuma, Chieko
    University of Massachusetts Medical School.
    Karlsson, Elinor
    Broad Institute.
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Genome-wide meta-analysis identifies inherited variation contributing to overall risk and age of onset in canine angiosarcomaManuscript (preprint) (Other academic)
  • 187.
    Mendelson, Michael M.
    et al.
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;Boston Univ, Sch Med, Boston, MA 02118 USA.;Boston Childrens Hosp, Dept Cardiol, Boston, MA USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Marioni, Riccardo E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia..
    Joehanes, Roby
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.;Harvard Med Sch, Hebrew SeniorLife, Boston, MA USA..
    Liu, Chunyu
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.;Boston Univ, Dept Biostat, Boston, MA USA..
    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.
    Aslibekyan, Stella
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA..
    Demerath, Ellen W.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Guan, Weihua
    Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA..
    Zhi, Degui
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Biostat, Birmingham, AL 35294 USA..
    Yao, Chen
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Huan, Tianxiao
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Willinger, Christine
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Chen, Brian
    NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Courchesne, Paul
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Multhaup, Michael
    Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA..
    Lrvin, Marguerite R.
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA..
    Cohain, Ariella
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Schadt, Eric E.
    Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA..
    Grove, Megan L.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Bressler, Jan
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    North, Kari
    Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC USA..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    Shah, Sonia
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    McRae, Allan F.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Harris, Sarah E.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh EH8 9YL, Midlothian, Scotland..
    Gibson, Jude
    Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil, Edinburgh EH8 9YL, Midlothian, Scotland..
    Redmond, Paul
    Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland..
    Coriey, Janie
    Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland..
    Murphy, Lee
    Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil, Edinburgh EH8 9YL, Midlothian, Scotland..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9YL, Midlothian, Scotland..
    Kleinbrink, Erica
    Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.;Wayne State Univ, Dept Neurol, Detroit, MI USA..
    Lipovich, Leonard
    Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA.;Wayne State Univ, Dept Neurol, Detroit, MI USA..
    Visscher, Peter M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Wray, Naomi R.
    Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.;Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia..
    Krauss, Ronald M.
    Childrens Hosp Oakland Res Inst, Oakland, CA USA..
    Fallin, Daniele
    Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA..
    Feinberg, Andrew
    Johns Hopkins Univ, Sch Med, Ctr Epigenet, Baltimore, MD USA..
    Absher, Devin M.
    HudsonAlpha Inst Biotechnol, Huntsville, AL USA..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Univ Texas Houston, Brown Fdn Inst Mol Med, Houston, TX USA..
    Pankow, James S.
    Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Fox, Caroline
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 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, Sch Med, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA..
    Arnett, Donna K.
    Univ Kentucky, Coll Publ Hlth, Lexington, KY USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Liang, Liming
    Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.;Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA..
    Levy, Daniel
    Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.;NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA..
    Deary, Lan J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9YL, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9YL, Midlothian, Scotland..
    Association of Body Mass Index with DNA Methylation and Gene Expression in Blood Cells and Relations to Cardiometabolic Disease: A Mendelian Randomization Approach2017In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 14, no 1, article id e1002215Article in journal (Refereed)
    Abstract [en]

    Background The link between DNA methylation, obesity, and adiposity-related diseases in the general population remains uncertain. Methods and Findings We conducted an association study of body mass index (BMI) and differential methylation for over 400,000 CpGs assayed by microarray in whole-blood-derived DNA from 3,743 participants in the Framingham Heart Study and the Lothian Birth Cohorts, with independent replication in three external cohorts of 4,055 participants. We examined variations in whole blood gene expression and conducted Mendelian randomization analyses to investigate the functional and clinical relevance of the findings. We identified novel and previously reported BMI-related differential methylation at 83 CpGs that replicated across cohorts; BMI-related differential methylation was associated with concurrent changes in the expression of genes in lipid metabolism pathways. Genetic instrumental variable analysis of alterations in methylation at one of the 83 replicated CpGs, cg11024682 (intronic to sterol regulatory element binding transcription factor 1 [SREBF1]), demonstrated links to BMI, adiposity-related traits, and coronary artery disease. Independent genetic instruments for expression of SREBF1 supported the findings linking methylation to adiposity and cardiometabolic disease. Methylation at a substantial proportion (16 of 83) of the identified loci was found to be secondary to differences in BMI. However, the cross-sectional nature of the data limits definitive causal determination. Conclusions We present robust associations of BMI with differential DNA methylation at numerous loci in blood cells. BMI-related DNA methylation and gene expression provide mechanistic insights into the relationship between DNA methylation, obesity, and adiposity-related diseases.

  • 188.
    Mitchell, Adam
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Wolk, Alicja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Type 2 Diabetes in Relation to Hip Bone Density, Area, and Bone Turnover in Swedish Men and Women: A Cross-Sectional Study2018In: Calcified Tissue International, ISSN 0171-967X, E-ISSN 1432-0827, Vol. 103, no 5, p. 501-511Article in journal (Refereed)
    Abstract [en]

    Men and women with type 2 diabetes mellitus (T2DM) have higher risk of hip fracture, but the mechanisms are not fully understood. We aimed to investigate how T2DM, glucose, and insulin were associated with femoral bone mineral density (BMD), bone mineral area (BMA), and bone turnover markers. We used two cross-sectional cohorts: the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 452, mean age 82 years) and the Swedish Mammography Cohort Clinical (SMCC, n = 4713, mean age 68 years). We identified men and women with normal fasting glucose (NFG), impaired fasting plasma glucose (IFG), and T2DM. BMD and BMA at the total hip and femoral shaft were measured using dual energy X-ray absorptiometry (DXA). Bone turnover markers; CrossLaps and osteocalcin were measured in women. Linear regression models were applied. Men and women showed a progressively higher BMD following the clinical cutoffs of fasting glucose from NFG to IFG to T2DM. In contrast, there was a progressively lower BMA. Men and women with T2DM, compared to those with NFG, had lower BMA at the total hip (- 1.7%; 95% CI - 3.2, - 0.2 and - 1.0%; 95% CI - 1.6, - 0.4) and the femoral shaft (- 2.0%; 95% CI - 3.5, - 0.4 and - 0.6%; 95% CI - 1.2, - 0.01), respectively. T2DM was associated with lower concentrations of CrossLaps (- 8.1%; 95% CI - 12.7, - 3.6) and osteocalcin (- 15.2%; 95% CI - 19.0, - 11.2). These cross-sectional results indicate that those with T2DM have smaller bone area and lower bone turnover, which could increase the risk of hip fracture.

  • 189.
    Mobacke, Ingrid
    et al.
    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.
    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.
    Circulating levels of perfluoroalkyl substances and left ventricular geometry of the heart in the elderly.2018In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 115, p. 295-300Article in journal (Refereed)
    Abstract [en]

    AIMS: Some persistent organic pollutants (POPs) such as hexachlorobenzene (HCB) and some polychlorinated biphenyls (PCBs) have been shown to interfere with myocardial function and geometry. We therefore investigated if also another group of POPs: per- and polyfluoroalkyl substances (PFASs) were associated with alterations in left ventricular geometry.

    METHODS: 801 subjects aged 70 years were investigated in a cross-sectional study within the scope of the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eight PFASs were detected in >75% of participants´ plasma by ultra-performance liquid chromatograph/tandem mass spectrometry. Left ventricular geometry was determined by echocardiography. Multivariable linear regression was used to investigate the associations between PFASs and left ventricular geometry of the heart after exclusion of subjects with previous myocardial infarction (n = 72).

    RESULTS: When adjusting for multiple comparisons, none of the eight PFASs evaluated were significantly related to left ventricular mass. However, perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA) were related to relative wall thickness (RWT) in a negative fashion (p < 0.0021). Besides being inversely related to RWT, PFNA was also positively related to left ventricular end-diastolic volume (LVEDD) (p < 0.0021). These analyses were adjusted for traditional cardiovascular risk factors.

    CONCLUSION: In this cross-sectional study, several of the PFASs evaluated, especially PFNA, were related to myocardial geometry: a reduction in relative wall thickness and an increase in left ventricular diameter following adjustment for traditional cardiovascular risk factors, suggesting a role for PFASs in cardiac remodeling.

  • 190. Morris, Andrew P
    et al.
    Le, Thu H
    Wu, Haojia
    Akbarov, Artur
    van der Most, Peter J
    Hemani, Gibran
    Smith, George Davey
    Mahajan, Anubha
    Gaulton, Kyle J
    Nadkarni, Girish N
    Valladares-Salgado, Adan
    Wacher-Rodarte, Niels
    Mychaleckyj, Josyf C
    Dueker, Nicole D
    Guo, Xiuqing
    Hai, Yang
    Haessler, Jeffrey
    Kamatani, Yoichiro
    Stilp, Adrienne M
    Zhu, Gu
    Cook, James P
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Center for Clinical Research Dalarna.
    Blanton, Susan H
    de Borst, Martin H
    Bottinger, Erwin P
    Buchanan, Thomas A
    Cechova, Sylvia
    Charchar, Fadi J
    Chu, Pei-Lun
    Damman, Jeffrey
    Eales, James
    Gharavi, Ali G
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Heath, Andrew C
    Ipp, Eli
    Kiryluk, Krzysztof
    Kramer, Holly J
    Kubo, Michiaki
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Lindgren, Cecilia M
    Lu, Yingchang
    Madden, Pamela A F
    Montgomery, Grant W
    Papanicolaou, George J
    Raffel, Leslie J
    Sacco, Ralph L
    Sanchez, Elena
    Stark, Holger
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Taylor, Kent D
    Xiang, Anny H
    Zivkovic, Aleksandra
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical 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 Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, Stanford Univ, Stanford Cardiovasc Inst, Stanford, USA; Stanford Univ, Stanford Diabet Res Ctr, Stanford, USA.
    Martin, Nicholas G
    Whitfield, John B
    Cai, Jianwen
    Laurie, Cathy C
    Okada, Yukinori
    Matsuda, Koichi
    Kooperberg, Charles
    Chen, Yii-Der Ida
    Rundek, Tatjana
    Rich, Stephen S
    Loos, Ruth J F
    Parra, Esteban J
    Cruz, Miguel
    Rotter, Jerome I
    Snieder, Harold
    Tomaszewski, Maciej
    Humphreys, Benjamin D
    Franceschini, Nora
    Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies2019In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, no 1, article id 29Article in journal (Refereed)
    Abstract [en]

    Chronic kidney disease (CKD) affects ~10% of the global population, with considerable ethnic differences in prevalence and aetiology. We assemble genome-wide association studies of estimated glomerular filtration rate (eGFR), a measure of kidney function that defines CKD, in 312,468 individuals of diverse ancestry. We identify 127 distinct association signals with homogeneous effects on eGFR across ancestries and enrichment in genomic annotations including kidney-specific histone modifications. Fine-mapping reveals 40 high-confidence variants driving eGFR associations and highlights putative causal genes with cell-type specific expression in glomerulus, and in proximal and distal nephron. Mendelian randomisation supports causal effects of eGFR on overall and cause-specific CKD, kidney stone formation, diastolic blood pressure and hypertension. These results define novel molecular mechanisms and putative causal genes for eGFR, offering insight into clinical outcomes and routes to CKD treatment development.

  • 191.
    Mubanga, Mwenya
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Dog Ownership and Cardiovascular Disease2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The relationship between pet ownership and human health has been studied extensively; however, the effect of dog ownership on human health has had conflicting results. The overall aim of this research project was to investigate the impact of dog ownership, and the death of the dog, on human cardiovascular health and all-cause mortality.

    Study I was a population-based study investigating the association between dog ownership with the risk of cardiovascular disease (CVD) and death. Of 3,432,153 individuals included, dog ownership (13.1%) was associated with a lower risk of CVD- and all-cause death by 23% and 20%, respectively. In single-person households, there was an inverse association between dog ownership and incident CVD, as well as a stronger inverse association with CVD-death and all-cause death.

    Study II was a population-based study investigating the association between dog ownership and initiation of treatment for cardiovascular risk factors in 2,026,865 adults. Dog ownership (14.6%) was associated with a slightly elevated risk of initiating treatment (2%) for hypertension and dyslipidaemia, but not for diabetes mellitus. However, some evidence for residual confounding was found.

    Study III investigated the risk of death after hospitalization for a first-ever acute myocardial infarction (n=181,696) or first-ever ischemic stroke (n=157,617) in two population-based cohorts. Dog ownership was associated with a 20% to 24% lower risk of all-cause mortality and CVD-death, respectively.

    In Study I-III, ownership of hunting breed dogs was associated with the lowest risk of the outcomes, while owning dogs of mixed pedigree was associated with worse cardiovascular health.

    Study IV found evidence of an increased risk of CVD after the loss of a life-insured pet (dog or cat; n=147,251) during the first week, 3-6 months after and 6-12 months after pet-loss.

    This thesis has used the Swedish population and health registers to investigate the relationship between various aspects of dog ownership and cardiovascular risk. By using defined, quantifiable end-points and robust statistical methods, this project has made an important contribution to the body of research underlying the positive relationship between dog ownership and cardiovascular health, paving the way for further research into causal mechanisms.

  • 192.
    Mubanga, Mwenya
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Egenvall, Agneta
    Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA..
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Dog ownership and mortality after a major cardiovascular event – a register-based prospective studyIn: International Journal of Epidemiology, ISSN 0300-5771, E-ISSN 1464-3685Article in journal (Refereed)
  • 193.
    Mubanga, Mwenya
    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.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Egenvall, Agneta
    Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Magnusson, Patrik K
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm.
    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. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA..
    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.
    Dog ownership and Cardiovascular Risk Factors: a nationwide prospective register-based cohort study2019In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 9, article id e023447Article in journal (Refereed)
    Abstract [en]

    Objective To study the association between dog ownership and cardiovascular risk factors.

    Design A nationwide register–based cohort study and a cross-sectional study in a subset.

    Setting A cohort of 2 026 865 participants was identified from the Register of the Total Population and linked to national registers for information on dog ownership, prescribed medication, hospital admissions, education level, income and country of birth. Participants were followed from 1 October, 2006, to the end of the study on 31 December, 2012, assessing medication for a cardiovascular risk factor, emigration and death. Cross-sectional associations were further assessed in 10 110 individuals from the TwinGene study with additional adjustment for professional level, employment status, Charlson comorbidity index, disability and tobacco use.

    Participants All Swedish residents aged 45–80 years on 1 October, 2006.

    Main outcome measures Initiation of medication for hypertension, dyslipidaemia and diabetes mellitus.

    Results After adjustment for confounders, the results indicated slightly higher likelihood of initiating antihypertensive (HR, 1.02; 95% CI, 1.01 to 1.03) and lipid-lowering treatment (HR, 1.02; 95% CI, 1.01 to 1.04) in dog owners than in non-owners, particularly among those aged 45–60 years and in those owning mixed breed or companion/toy breed dogs. No association of dog ownership with initiation of treatment for diabetes was found in the overall analysis (HR, 0.98; 95% CI, 0.95 to 1.01). Sensitivity analyses in the TwinGene cohort indicated confounding of the association between dog ownership and prevalent treatment for hypertension, dyslipidaemia and diabetes mellitus, respectively, from factors not available in the national cohort, such as employment status and non cardiovascularchronic disease status.

    Conclusions In this large cohort study, dog ownership was associated with a minimally higher risk of initiation of treatment for hypertension and dyslipidaemia implying that the previously reported lower risk of cardiovascular mortality among dog owners in this cohort is not explained by reduced hypertension and dyslipidaemia. These observations may suffer from residual confounding despite access to multiple important covariates, and future studies may add valuable information.

  • 194.
    Mubanga, Mwenya
    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.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    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. Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden.
    Egenvall, Agneta
    Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Magnusson, Patrik K
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 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. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA.
    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 ownership and the risk of cardiovascular disease and death: a nationwide cohort study2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, no 1, article id 15821Article in journal (Refereed)
    Abstract [en]

    Dogs may be beneficial in reducing cardiovascular risk in their owners by providing social support and motivation for physical activity. We aimed to investigate the association of dog ownership with incident cardiovascular disease (CVD) and death in a register-based prospective nation-wide cohort (n = 3,432,153) with up to 12 years of follow-up. Self-reported health and lifestyle habits were available for 34,202 participants in the Swedish Twin Register. Time-to-event analyses with time-updated covariates were used to calculate hazard ratios (HR) with 95% confidence intervals (CI). In single- and multiple-person households, dog ownership (13.1%) was associated with lower risk of death, HR 0.67 (95% CI, 0.65-0.69) and 0.89 (0.87-0.91), respectively; and CVD death, HR 0.64 (0.59-0.70), and 0.85 (0.81-0.90), respectively. In single-person households, dog ownership was inversely associated with cardiovascular outcomes (HR composite CVD 0.92, 95% CI, 0.89-0.94). Ownership of hunting breed dogs was associated with lowest risk of CVD. Further analysis in the Twin Register could not replicate the reduced risk of CVD or death but also gave no indication of confounding by disability, comorbidities or lifestyle factors. In conclusion, dog ownership appears to be associated with lower risk of CVD in single-person households and lower mortality in the general population.

  • 195.
    Mubanga, Mwenya
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Mariosa, Daniela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Egenvall, Agneta
    Department of Clinical Sciences, Division of Ruminant Medicine and Veterinary Epidemiology, Swedish University of Agricultural Sciences.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA..
    Fang, Fang
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm. Sweden..
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    The impact of death of a pet on major acute cardiovascular risk in the owner: a register-based cohort studyManuscript (preprint) (Other academic)
  • 196. Murray, Christopher J L
    et al.
    Ortblad, Katrina F
    Guinovart, Caterina
    Lim, Stephen S
    Wolock, Timothy M
    Roberts, D Allen
    Dansereau, Emily A
    Graetz, Nicholas
    Barber, Ryan M
    Brown, Jonathan C
    Wang, Haidong
    Duber, Herbert C
    Naghavi, Mohsen
    Dicker, Daniel
    Dandona, Lalit
    Salomon, Joshua A
    Heuton, Kyle R
    Foreman, Kyle
    Phillips, David E
    Fleming, Thomas D
    Flaxman, Abraham D
    Phillips, Bryan K
    Johnson, Elizabeth K
    Coggeshall, Megan S
    Abd-Allah, Foad
    Abera, Semaw Ferede
    Abraham, Jerry P
    Abubakar, Ibrahim
    Abu-Raddad, Laith J
    Abu-Rmeileh, Niveen Me
    Achoki, Tom
    Adeyemo, Austine Olufemi
    Adou, Arsène Kouablan
    Adsuar, José C
    Agardh, Emilie Elisabet
    Akena, Dickens
    Al Kahbouri, Mazin J
    Alasfoor, Deena
    Albittar, Mohammed I
    Alcalá-Cerra, Gabriel
    Alegretti, Miguel Angel
    Alemu, Zewdie Aderaw
    Alfonso-Cristancho, Rafael
    Alhabib, Samia
    Ali, Raghib
    Alla, Francois
    Allen, Peter J
    Alsharif, Ubai
    Alvarez, Elena
    Alvis-Guzman, Nelson
    Amankwaa, Adansi A
    Amare, Azmeraw T
    Amini, Hassan
    Ammar, Walid
    Anderson, Benjamin O
    Antonio, Carl Abelardo T
    Anwari, Palwasha
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Arsenijevic, Valentina S Arsic
    Artaman, Ali
    Asghar, Rana J
    Assadi, Reza
    Atkins, Lydia S
    Badawi, Alaa
    Balakrishnan, Kalpana
    Banerjee, Amitava
    Basu, Sanjay
    Beardsley, Justin
    Bekele, Tolesa
    Bell, Michelle L
    Bernabe, Eduardo
    Beyene, Tariku Jibat
    Bhala, Neeraj
    Bhalla, Ashish
    Bhutta, Zulfiqar A
    Abdulhak, Aref Bin
    Binagwaho, Agnes
    Blore, Jed D
    Bose, Dipan
    Brainin, Michael
    Breitborde, Nicholas
    Castañeda-Orjuela, Carlos A
    Catalá-López, Ferrán
    Chadha, Vineet K
    Chang, Jung-Chen
    Chiang, Peggy Pei-Chia
    Chuang, Ting-Wu
    Colomar, Mercedes
    Cooper, Leslie Trumbull
    Cooper, Cyrus
    Courville, Karen J
    Cowie, Benjamin C
    Criqui, Michael H
    Dandona, Rakhi
    Dayama, Anand
    De Leo, Diego
    Degenhardt, Louisa
    Del Pozo-Cruz, Borja
    Deribe, Kebede
    Des Jarlais, Don C
    Dessalegn, Muluken
    Dharmaratne, Samath D
    Dilmen, Uğur
    Ding, Eric L
    Driscoll, Tim R
    Durrani, Adnan M
    Ellenbogen, Richard G
    Ermakov, Sergey Petrovich
    Esteghamati, Alireza
    Faraon, Emerito Jose A
    Farzadfar, Farshad
    Fereshtehnejad, Seyed-Mohammad
    Fijabi, Daniel Obadare
    Forouzanfar, Mohammad H
    Fra Paleo, Urbano
    Gaffikin, Lynne
    Gamkrelidze, Amiran
    Gankpé, Fortuné Gbètoho
    Geleijnse, Johanna M
    Gessner, Bradford D
    Gibney, Katherine B
    Ginawi, Ibrahim Abdelmageem Mohamed
    Glaser, Elizabeth L
    Gona, Philimon
    Goto, Atsushi
    Gouda, Hebe N
    Gugnani, Harish Chander
    Gupta, Rajeev
    Gupta, Rahul
    Hafezi-Nejad, Nima
    Hamadeh, Randah Ribhi
    Hammami, Mouhanad
    Hankey, Graeme J
    Harb, Hilda L
    Haro, Josep Maria
    Havmoeller, Rasmus
    Hay, Simon I
    Hedayati, Mohammad T
    Pi, Ileana B Heredia
    Hoek, Hans W
    Hornberger, John C
    Hosgood, H Dean
    Hotez, Peter J
    Hoy, Damian G
    Huang, John J
    Iburg, Kim M
    Idrisov, Bulat T
    Innos, Kaire
    Jacobsen, Kathryn H
    Jeemon, Panniyammakal
    Jensen, Paul N
    Jha, Vivekanand
    Jiang, Guohong
    Jonas, Jost B
    Juel, Knud
    Kan, Haidong
    Kankindi, Ida
    Karam, Nadim E
    Karch, André
    Karema, Corine Kakizi
    Kaul, Anil
    Kawakami, Norito
    Kazi, Dhruv S
    Kemp, Andrew H
    Kengne, Andre Pascal
    Keren, Andre
    Kereselidze, Maia
    Khader, Yousef Saleh
    Khalifa, Shams Eldin Ali Hassan
    Khan, Ejaz Ahmed
    Khang, Young-Ho
    Khonelidze, Irma
    Kinfu, Yohannes
    Kinge, Jonas M
    Knibbs, Luke
    Kokubo, Yoshihiro
    Kosen, S
    Defo, Barthelemy Kuate
    Kulkarni, Veena S
    Kulkarni, Chanda
    Kumar, Kaushalendra
    Kumar, Ravi B
    Kumar, G Anil
    Kwan, Gene F
    Lai, Taavi
    Balaji, Arjun Lakshmana
    Lam, Hilton
    Lan, Qing
    Lansingh, Van C
    Larson, Heidi J
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lee, Jong-Tae
    Leigh, James
    Leinsalu, Mall
    Leung, Ricky
    Li, Yichong
    Li, Yongmei
    De Lima, Graça Maria Ferreira
    Lin, Hsien-Ho
    Lipshultz, Steven E
    Liu, Shiwei
    Liu, Yang
    Lloyd, Belinda K
    Lotufo, Paulo A
    Machado, Vasco Manuel Pedro
    Maclachlan, Jennifer H
    Magis-Rodriguez, Carlos
    Majdan, Marek
    Mapoma, Christopher Chabila
    Marcenes, Wagner
    Marzan, Melvin Barrientos
    Masci, Joseph R
    Mashal, Mohammad Taufiq
    Mason-Jones, Amanda J
    Mayosi, Bongani M
    Mazorodze, Tasara T
    Mckay, Abigail Cecilia
    Meaney, Peter A
    Mehndiratta, Man Mohan
    Mejia-Rodriguez, Fabiola
    Melaku, Yohannes Adama
    Memish, Ziad A
    Mendoza, Walter
    Miller, Ted R
    Mills, Edward J
    Mohammad, Karzan Abdulmuhsin
    Mokdad, Ali H
    Mola, Glen Liddell
    Monasta, Lorenzo
    Montico, Marcella
    Moore, Ami R
    Mori, Rintaro
    Moturi, Wilkister Nyaora
    Mukaigawara, Mitsuru
    Murthy, Kinnari S
    Naheed, Aliya
    Naidoo, Kovin S
    Naldi, Luigi
    Nangia, Vinay
    Narayan, K M Venkat
    Nash, Denis
    Nejjari, Chakib
    Nelson, Robert G
    Neupane, Sudan Prasad
    Newton, Charles R
    Ng, Marie
    Nisar, Muhammad Imran
    Nolte, Sandra
    Norheim, Ole F
    Nowaseb, Vincent
    Nyakarahuka, Luke
    Oh, In-Hwan
    Ohkubo, Takayoshi
    Olusanya, Bolajoko O
    Omer, Saad B
    Opio, John Nelson
    Orisakwe, Orish Ebere
    Pandian, Jeyaraj D
    Papachristou, Christina
    Caicedo, Angel J Paternina
    Patten, Scott B
    Paul, Vinod K
    Pavlin, Boris Igor
    Pearce, Neil
    Pereira, David M
    Pervaiz, Aslam
    Pesudovs, Konrad
    Petzold, Max
    Pourmalek, Farshad
    Qato, Dima
    Quezada, Amado D
    Quistberg, D Alex
    Rafay, Anwar
    Rahimi, Kazem
    Rahimi-Movaghar, Vafa
    Rahman, Sajjad Ur
    Raju, Murugesan
    Rana, Saleem M
    Razavi, Homie
    Reilly, Robert Quentin
    Remuzzi, Giuseppe
    Richardus, Jan Hendrik
    Ronfani, Luca
    Roy, Nobhojit
    Sabin, Nsanzimana
    Saeedi, Mohammad Yahya
    Sahraian, Mohammad Ali
    Samonte, Genesis May J
    Sawhney, Monika
    Schneider, Ione J C
    Schwebel, David C
    Seedat, Soraya
    Sepanlou, Sadaf G
    Servan-Mori, Edson E
    Sheikhbahaei, Sara
    Shibuya, Kenji
    Shin, Hwashin Hyun
    Shiue, Ivy
    Shivakoti, Rupak
    Sigfusdottir, Inga Dora
    Silberberg, Donald H
    Silva, Andrea P
    Simard, Edgar P
    Singh, Jasvinder A
    Skirbekk, Vegard
    Sliwa, Karen
    Soneji, Samir
    Soshnikov, Sergey S
    Sreeramareddy, Chandrashekhar T
    Stathopoulou, Vasiliki Kalliopi
    Stroumpoulis, Konstantinos
    Swaminathan, Soumya
    Sykes, Bryan L
    Tabb, Karen M
    Talongwa, Roberto Tchio
    Tenkorang, Eric Yeboah
    Terkawi, Abdullah Sulieman
    Thomson, Alan J
    Thorne-Lyman, Andrew L
    Towbin, Jeffrey A
    Traebert, Jefferson
    Tran, Bach X
    Dimbuene, Zacharie Tsala
    Tsilimbaris, Miltiadis
    Uchendu, Uche S
    Ukwaja, Kingsley N
    Vallely, Andrew J
    Vasankari, Tommi J
    Venketasubramanian, N
    Violante, Francesco S
    Vlassov, Vasiliy Victorovich
    Waller, Stephen
    Wallin, Mitchell T
    Wang, Linhong
    Wang, Sharon Xiaorong
    Wang, Yanping
    Weichenthal, Scott
    Weiderpass, Elisabete
    Weintraub, Robert G
    Westerman, Ronny
    White, Richard A
    Wilkinson, James D
    Williams, Thomas Neil
    Woldeyohannes, Solomon Meseret
    Wong, John Q
    Xu, Gelin
    Yang, Yang C
    Yano, Yuichiro
    Yip, Paul
    Yonemoto, Naohiro
    Yoon, Seok-Jun
    Younis, Mustafa
    Yu, Chuanhua
    Jin, Kim Yun
    El Sayed Zaki, Maysaa
    Zhao, Yong
    Zheng, Yingfeng
    Zhou, Maigeng
    Zhu, Jun
    Zou, Xiao Nong
    Lopez, Alan D
    Vos, Theo
    Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 20132014In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, no 9947, p. 1005-1070Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration.

    METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.

    FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million