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      • Record: found
      • Abstract: found
      • Article: found

      Common variants associated with plasma triglycerides and risk for coronary artery disease

      research-article
      Author(s): 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 6 , 8 , 1 , 2 , 4 , 2 , 4 , 9 , 10 , 11 , 12 ,   10 , 11 , 13 , 8 , 14 , 15 , 16 , 17 , 18 , 8 , 19 , 20 , 21 , 22 , 23 , 24 , 4 , 25 , 26 , 27 , 28 , 25 , 4 , 29 , 30 , 12 , 30 , 31 , 32 , 20 , 33 , 8 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 13 , 48 , 25 , 26 , 49 , 50 , 51 , 52 , 53 , 49 , 4 , 54 , 55 , 25 , 40 , 41 , 50 , 56 , 2 , 57 , 58 , 59 , 60 , 61 ,   8 , 56 , 62 , 10 , 11 , 13 , 63 , 64 , 40 , 41 , 65 , 8 , 66 , 21 , 67 , 68 , 69 , 70 , 71 , 14 , 72 , 73 , 70 , 74 , 12 , 75 , 76 , 29 , 77 , 78 , 79 , 80 , 81 , 22 , 82 , 83 , 39 , 72 , 84 , 79 , 85 , 86 , 87 , 88 , 76 , 89 , 90 , 91 , 92 , 93 , 94 , 66 , 95 , 88 , 96 , 87 , 74 , 97 , 98 , 44 , 88 , 96 , 99 , 58 , 45 , 46 , 47 , 100 , 101 , 45 , 102 , 103 , 104 , 23 , 105 , 82 , 49 , 106 , 107 , 77 , 108 , 109 , 110 , 74 , 111 , 45 , 71 , 40 , 112 , 113 , 12 , 30 , 114 , 12 , 30 , 91 , 115 , 116 , 117 , 116 , 117 , 15 , 16 , 118 , 119 , 120 , 29 , 121 , 122 , 123 , 124 , 74 , 125 , 40 , 41 , 126 , 12 , 77 , 127 , 118 , 119 , 120 , 128 , 129 , 4 , 54 , 55 , 12 , 30 , 129 , 130 , 29 , 131 , 132 , 29 , 12 , 30 , 45 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 131 , 27 , 141 , 138 , 142 , 143 , 29 , 24 , 72 , 73 , 144 , 145 , 146 , 77 , 147 , 30 , 81 , 86 , 148 , 149 , 65 , 57 , 150 , 50 , 151 , 152 , 153 , 34 , 63 , 64 , 154 , 155 , 58 , 4 , 54 , 55 , 118 , 120 , 97 , 156 , 157 , 158 , 159 , 160 , 38 , 39 , 72 , 84 , 115 , 161 , 162 , 163 , 31 , 40 , 164 , 165 ,   58 , 73 , 144 , 166 , 21 , 167 , 71 , 168 , 169 , 170 , 168 , 99 , 171 , 172 , 28 , 173 , 43 , 124 , 174 , 28 , 89 , 175 , 176 , 25 , 26 , 177 , 22 , 36 , 37 , 132 , 13 , 32 , 94 , 178 , 179 , 29 , 180 , 181 , 135 , 99 , 182 , 30 , 183 , 184 , 185 , 76 , 186 , 141 , 187 , 188 , 49 , 189 , 10 , 35 , 172 , 48 , 66 , 190 , 191 , 147 , 192 , 101 , 193 , 194 , 195 , 196 , 197 , 20 , 33 , 198 , 35 , 172 , 45 , 173 , 129 , 199 , 2 , 3 , 4 , 200 , 201 , 202 , 69 , 22 , 66 , 190 , 15 , 16 , 44 , 59 , 61 , 203 , 12 , 40 , 41 , 9 , 204 , 12 , 30 , 205 , 8 , 12 , 14 , 10 , 11 , 28 , 8 , 2 , 4 , 206 , 2 , 4 , 206 , 1 , 2 , 3 , 4
      Publication date (Electronic):
      Journal: Nature genetics

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          Abstract

          Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiologic studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids ( P<5×10 −8 for each) to examine the role of triglycerides on risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglycerides, and show that the direction and magnitude of both are factors in determining CAD risk. Second, we consider loci with only a strong magnitude of association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol, a polymorphism's strength of effect on triglycerides is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

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          Most cited references36

          • Record: found
          • Abstract: found
          • Article: not found

          'Mendelian randomization': can genetic epidemiology contribute to understanding environmental determinants of disease?

          George Davey Smith, Shah Ebrahim (2003)
          Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading, despite our best efforts to improve the design and analysis of studies. Mendelian randomization-the random assortment of genes from parents to offspring that occurs during gamete formation and conception-provides one method for assessing the causal nature of some environmental exposures. The association between a disease and a polymorphism that mimics the biological link between a proposed exposure and disease is not generally susceptible to the reverse causation or confounding that may distort interpretations of conventional observational studies. Several examples where the phenotypic effects of polymorphisms are well documented provide encouraging evidence of the explanatory power of Mendelian randomization and are described. The limitations of the approach include confounding by polymorphisms in linkage disequilibrium with the polymorphism under study, that polymorphisms may have several phenotypic effects associated with disease, the lack of suitable polymorphisms for studying modifiable exposures of interest, and canalization-the buffering of the effects of genetic variation during development. Nevertheless, Mendelian randomization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to understanding and preventing the adverse effects on human health of modifiable exposures.
          Article 0 comments Cited 1002 times – based on 0 reviews     Review now
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            • Abstract: not found
            • Article: not found

            ‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?*

            Shah Ebrahim, Shah Ebrahim (2003)
            Article 0 comments Cited 958 times – based on 0 reviews     Review now
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              • Record: found
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              • Article: not found

              Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study.

              Christopher Murray, Alan Lopez (1997)
              Prevention and control of disease and injury require information about the leading medical causes of illness and exposures or risk factors. The assessment of the public-health importance of these has been hampered by the lack of common methods to investigate the overall, worldwide burden. The Global Burden of Disease Study (GBD) provides a standardised approach to epidemiological assessment and uses a standard unit, the disability-adjusted life year (DALY), to aid comparisons. DALYs for each age-sex group in each GBD region for 107 disorders were calculated, based on the estimates of mortality by cause, incidence, average age of onset, duration, and disability severity. Estimates of the burden and prevalence of exposure in different regions of disorders attributable to malnutrition, poor water supply, sanitation and personal and domestic hygiene, unsafe sex, tobacco use, alcohol, occupation, hypertension, physical inactivity, use of illicit drugs, and air pollution were developed. Developed regions account for 11.6% of the worldwide burden from all causes of death and disability, and account for 90.2% of health expenditure worldwide. Communicable, maternal, perinatal, and nutritional disorders explain 43.9%; non-communicable causes 40.9%; injuries 15.1%; malignant neoplasms 5.1%; neuropsychiatric conditions 10.5%; and cardiovascular conditions 9.7% of DALYs worldwide. The ten leading specific causes of global DALYs are, in descending order, lower respiratory infections, diarrhoeal diseases, perinatal disorders, unipolar major depression, ischaemic heart disease, cerebrovascular disease, tuberculosis, measles, road-traffic accidents, and congenital anomalies. 15.9% of DALYs worldwide are attributable to childhood malnutrition and 6.8% to poor water, and sanitation and personal and domestic hygiene. The three leading contributors to the burden of disease are communicable and perinatal disorders affecting children. The substantial burdens of neuropsychiatric disorders and injuries are under-recognised. The epidemiological transition in terms of DALYs has progressed substantially in China, Latin America and the Caribbean, other Asia and islands, and the middle eastern crescent. If the burdens of disability and death are taken into account, our list differs substantially from other lists of the leading causes of death. DALYs provide a common metric to aid meaningful comparison of the burden of risk factors, diseases, and injuries.
              Article 0 comments Cited 803 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 9216904
                Journal ID (pubmed-jr-id): 2419
                Journal ID (nlm-ta): Nat Genet
                Journal ID (iso-abbrev): Nat. Genet.
                Title: Nature genetics
                ISSN (Print): 1061-4036
                ISSN (Electronic): 1546-1718
                Publication date Nihms-submitted: 3 December 2013
                Publication date (Electronic): 06 October 2013
                Publication date (Print): November 2013
                Publication date PMC-release: 01 May 2014
                Volume: 45
                Issue: 11
                Pages: 1345-1352
                Affiliations
                [1 ]Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
                [2 ]Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
                [3 ]Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
                [4 ]Program in Medical and Population Genetics, Broad Institute, 7 Cambridge Center, Cambridge, MA 02142, USA
                [5 ]Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
                [6 ]Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA
                [7 ]Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA
                [8 ]Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA
                [9 ]Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA
                [10 ]Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden
                [11 ]Science for Life Laboratory, Uppsala University, Uppsala, Sweden
                [12 ]Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA, Hinxton, United Kingdom
                [13 ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
                [14 ]Department of Genetics, University of North Carolina, Chapel Hill, NC 27599 USA
                [15 ]Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Ave., Boston MA 02215, USA
                [16 ]Harvard Medical School, Boston MA 02115, USA
                [17 ]Service of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland
                [18 ]Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
                [19 ]Division of Preventive Medicine and Health Services Research, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
                [20 ]Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands
                [21 ]Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
                [22 ]Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School. Dundee, DD1 9SY, United Kingdom
                [23 ]Cardiology, Department of Specialities of Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland
                [24 ]Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
                [25 ]Estonian Genome Center of the University of Tartu, Tartu, Estonia
                [26 ]Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
                [27 ]Department of Genetics, Washington University School of Medicine, USA
                [28 ]Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom
                [29 ]Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, United Kingdom
                [30 ]Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
                [31 ]Hjelt Institute, Department of Public Health, University of Helsinki, Finland
                [32 ]Centre For Paediatric Epidemiology and Biostatistics/MRC Centre of Epidemiology for Child Health, University College of London Institute of Child Health, London, United Kingdom
                [33 ]Centre for Medical Systems Biology, Leiden, the Netherlands
                [34 ]Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
                [35 ]Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
                [36 ]Genome Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
                [37 ]Clinical Pharmacology, NIHR Cardiovascular Biomedical Research Unit, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry Queen Mary University of London, London, UK
                [38 ]Biocenter Oulu, University of Oulu, Oulu, Finland
                [39 ]Institute of Health Sciences, University of Oulu, Finland
                [40 ]Institute for Molecular Medicine Finland FIMM, University of Helsinki, Finland
                [41 ]Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
                [42 ]Department of Internal Medicine II – Cardiology, University of Ulm Medical Centre, Ulm, Germany
                [43 ]Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty of Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 7-11, 68167 Mannheim, Germany
                [44 ]Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
                [45 ]MRC Epidemiology Unit, Institute of Metabolic Science, Box 285, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom
                [46 ]Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland
                [47 ]Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland
                [48 ]Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
                [49 ]Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland, School of Medicine, Baltimore, Maryland
                [50 ]Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany
                [51 ]Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians University, Munich, Germany
                [52 ]Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Munich, Germany
                [53 ]Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands
                [54 ]Division of Endocrinology, Children's Hospital Boston, Boston, Massachusetts 02115, USA
                [55 ]Division of Genetics, Program in Genomics, Children's Hospital Boston, Boston, Massachusetts 02115, USA
                [56 ]Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche, Monserrato, 09042, Italy
                [57 ]Center for Neurobehavioral Genetics, The Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA
                [58 ]Genetic Epidemiology Group, Deparment of Epidemiology and Public Health, UCL, London WC1E 6BT, United Kingdom
                [59 ]Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Center, Scania University Hosptial, Malmö, Sweden
                [60 ]Department of Odontology, Umeå University, Umeå, Sweden
                [61 ]Department of Public Health and Primary Care, Unit of Medicine, Umeå University, Umeå, Sweden
                [62 ]Dipartimento di Scienze Biomediche, Universita di Sassari, 07100 SS, Italy
                [63 ]Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
                [64 ]Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
                [65 ]Clinical Research Branch, National Institute Health, Baltimore, MD, USA
                [66 ]deCODE Genetics/Amgen, 101 Reykjavik, Iceland
                [67 ]Department of Genetics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA
                [68 ]Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA
                [69 ]Human Genetics Center, University of Texas Health Science Center - School of Public Health, Houston, TX 77030, USA
                [70 ]HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA
                [71 ]MRC Unit for Lifelong Health and Ageing, 33 Bedford Place, London, WC1B 5JU, United Kingdom
                [72 ]Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
                [73 ]Ealing Hospital, Southall, Middlesex UB1 3HW, United Kingdom
                [74 ]MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda
                [75 ]University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Level 4, Institute of Metabolic Science Box 289 Addenbrooke's Hospital Cambridge CB2 OQQ, UK
                [76 ]Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
                [77 ]Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA
                [78 ]Department of Experimental Medicine, University of Milano Bicocca, Italy
                [79 ]MedStar Health Research Institute, 6525 Belcrest Road, Suite 700, Hyattsville, MD 20782, USA
                [80 ]Research Centre on Public Health, University of Milano Bicocca, Italy
                [81 ]Department of Dietetics-Nutrition, Harokopio University, 70 El. Venizelou Str, Athens, Greece
                [82 ]Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg 85764, Germany
                [83 ]Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg 85764, Germany
                [84 ]MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, UK
                [85 ]The Laboratory in Mjodd, 108 Reykjavik, Iceland
                [86 ]Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
                [87 ]Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
                [88 ]Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany
                [89 ]Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, OX3 7LJ, United Kingdom
                [90 ]Department of Public Health and Clinical Medicine, Nutritional research, Umeå University, Umeå, Sweden
                [91 ]Department of Clinical Sciences/Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland
                [92 ]MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, United Kingdom
                [93 ]Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
                [94 ]Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany
                [95 ]Division of Endocrinology & Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
                [96 ]Hannover Unified Biobank, Hannover Medical School, Hannover 30625, Germany
                [97 ]Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
                [98 ]Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom
                [99 ]Kuopio Research Institute of Exercise Medicine, Kuopio, Finland
                [100 ]Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, School of Medicine, National Yang-Ming University, Taipei, Taiwan
                [101 ]Diabetes Prevention Unit, National Institute for Health and Welfare, 00271 Helsinki, Finland
                [102 ]The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, USA
                [103 ]The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, USA
                [104 ]The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York
                [105 ]School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom
                [106 ]Institute for Medical Informatics and Biometrics, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany
                [107 ]Laboratory of Genetics, National Institute on Aging, Baltimore, MD21224, USA
                [108 ]Department of Clinical Pharmacology, University of Tampere School of Medicine, Tampere 33014, Finland
                [109 ]Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland
                [110 ]Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland
                [111 ]Department of Clinical Biochemistry, Landspitali University Hospital, 101 Reykjavik, Iceland
                [112 ]Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
                [113 ]Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United Kingdom
                [114 ]Department of Statistical Sciences, University College of London, London, United Kingdom
                [115 ]National Institute for Health and Welfare, Oulu, Finland
                [116 ]Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Blvd, Building 421, Translational Research Center, Philadelphia, PA 19104-5158, USA
                [117 ]Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Blvd, Building 421, Translational Research Center, Philadelphia, PA 19104-5158, USA
                [118 ]Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
                [119 ]Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
                [120 ]Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging (NCHA), Leiden, The Netherlands
                [121 ]Department of Clinical Sciences/Clinical Chemistry, University of Oulu, Oulu, Finland
                [122 ]National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK
                [123 ]Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK
                [124 ]Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria
                [125 ]School of International Development, University of East Anglia, Norwich NR4 7TJ, United Kingdom
                [126 ]University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland
                [127 ]INSERM UMRS 937, Pierre and Marie Curie University, Paris, France
                [128 ]Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, The Netherlands
                [129 ]LifeLines Cohort Study, University of Groningen, University Medical Center Groningen, The Netherlands
                [130 ]Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands
                [131 ]Department of Biological Psychology, VU Univ, Amsterdam, The Netherlands
                [132 ]Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway
                [133 ]Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA
                [134 ]Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Faculty of Medicine, Strasbourg, France
                [135 ]Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
                [136 ]Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy
                [137 ]Chemical Pathology, Department of Pathology, University of the West Indies, Mona, Kingston 7, Jamaica
                [138 ]Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Route de la Corniche 10, 1010 Lausanne, Switzerland
                [139 ]Division of Endocrinology and Diabetes, Department of Internal Medicine, Ulm University Medical Centre, Ulm, Germany
                [140 ]Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
                [141 ]Department of Medicine III, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany
                [142 ]Ministry of Health, Victoria, Republic of Seychelles
                [143 ]Service of Nephrology, Lausanne University Hospital, Lausanne, Switzerland
                [144 ]Imperial College Healthcare NHS Trust, London, United Kingdom
                [145 ]Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA
                [146 ]Department of Medicine, University of California Los Angeles, Los Angeles, California, USA
                [147 ]Department of Preventive Medicine and Epidemiology, Loyola University Medical School, Maywood, Illinois 60153, USA
                [148 ]Office of Population Studies Foundation, University of San Carlos, Talamban, Cebu City, Philippines
                [149 ]Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France
                [150 ]Department of Psychiatry, University of California, Los Angeles, USA
                [151 ]Department of Clinical Sciences, Lund University, SE-20502, Malmö, Sweden
                [152 ]Department of Medicine, Helsinki University Hospital, FI-00029 Helsinki, Finland
                [153 ]Icelandic Heart Association, Kopavogur, Iceland
                [154 ]Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
                [155 ]Laboratory of Epidemiology, Demography, and Biometry, National Institute on Ageing, Bethesda, MD, USA
                [156 ]Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
                [157 ]Cardiovascular Genetics, BHF Laboratories, Institute Cardiovascular Science, University College London, London, United Kingdom
                [158 ]Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA
                [159 ]HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway
                [160 ]Kaiser Permanente, Division of Research, Oakland, CA, USA
                [161 ]Unit of Primary Care, Oulu University Hospital, Oulu, Finland
                [162 ]Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland
                [163 ]Department of Clinical Physiology, University of Tampere School of Medicine, Tampere 33014, Finland
                [164 ]Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
                [165 ]Institute of Clinical Medicine, Department of Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, Finland
                [166 ]National Heart & Lung Institute, Imperial College London, Hammersmith Hospital, London, United Kingdom
                [167 ]Children's Hospital Oakland Research Institute, 5700 Martin Luther King Junior Way, Oakland, CA 94609, USA
                [168 ]Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland
                [169 ]Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark
                [170 ]Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark
                [171 ]Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Finland
                [172 ]Department of Medical Sciences, Uppsala University, Uppsala, Sweden
                [173 ]Queensland Institute of Medical Research, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia
                [174 ]Synlab Academy, Synlab Services GmbH, Gottlieb-Daimler-Straβe 25, 68165 Mannheim, Germany
                [175 ]Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston 7, Jamaica
                [176 ]U872 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, 75006 Paris, France
                [177 ]Department of Medicine, Kuopio University Hospital, Kuopio, Finland
                [178 ]Department of Neurology, General Central Hospital, Bolzano, Italy
                [179 ]Department of Neurology, University of Lübeck, Lübeck, Germany
                [180 ]Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA
                [181 ]Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA
                [182 ]Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland
                [183 ]Center for Non-Communicable Diseases, Karachi, Pakistan
                [184 ]Department of Medicine, University of Pennsylvania, USA
                [185 ]Unit of Chronic Disease Epidemiology and Prevention, National Institute for Health and Welfare, Helsinki, Finland
                [186 ]South Karelia Central Hospital, Lappeenranta, Finland
                [187 ]Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany
                [188 ]Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
                [189 ]Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland
                [190 ]Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland
                [191 ]Division of Population Health Sciences and Education, St George's, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom
                [192 ]Department of Pharmacological Sciences, University of Milan, Monzino Cardiology Center, IRCCS, Milan, Italy
                [193 ]Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria
                [194 ]King Abdulaziz University, Faculty of Medicine, Jeddah 21589, Saudi Arabia
                [195 ]Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, 28046
                [196 ]Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland
                [197 ]Research Unit, Kuopio University Hospital, Kuopio, Finland
                [198 ]Department of Medicine, Lausanne University Hospital, Switzerland
                [199 ]Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands
                [200 ]Department of Cardiovascular Epidemiology and Population Genetics, National Center for Cardiovascular Investigation, Madrid, Spain
                [201 ]IMDEA-Alimentacion, Madrid, Spain
                [202 ]Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
                [203 ]Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
                [204 ]Framingham Heart Study, Framingham, MA, USA
                [205 ]Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA
                [206 ]Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02138, USA
                Author notes
                [† ]Correspondence to: Sekar Kathiresan, M.D. skathiresan@ 123456partners.org or Benjamin M. Neale, Ph.D. bneale@ 123456broadinstitute.org or Mark J. Daly, Ph.D. mjdaly@ 123456atgu.mgh.harvard.edu
                [*]

                Denotes equal contribution

                Article
                Manuscript ID: NIHMS524704
                DOI: 10.1038/ng.2795
                PMC ID: 3904346
                PubMed ID: 24097064
                SO-VID: 165cc7fa-8683-4483-8457-47e13b4c9651
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                Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

                History
                Funding
                Funded by: National Heart, Lung, and Blood Institute : NHLBI
                Award ID: R01 HL107816 || HL
                Categories
                Subject: Article

                ScienceOpen disciplines: Genetics
                Data availability:
                ScienceOpen disciplines: Genetics

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