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

      Discovery and Refinement of Loci Associated with Lipid Levels

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

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and total cholesterol are heritable, modifiable, risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,578 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5×10 −8, including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian, and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipids are often associated with cardiovascular and metabolic traits including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio, and body mass index. Our results illustrate the value of genetic data from individuals of diverse ancestries and provide insights into biological mechanisms regulating blood lipids to guide future genetic, biological, and therapeutic research.

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          Most cited references52

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          • Abstract: not found
          • Article: not found

          Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.

          William T. Friedewald, Robert Levy, Donald Fredrickson (1972)
          Article 0 comments Cited 1868 times – based on 0 reviews     Review now
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            • Record: found
            • Abstract: found
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            Principal components analysis corrects for stratification in genome-wide association studies.

            Alkes L. Price, Nick Patterson, Robert Plenge … (2006)
            Population stratification--allele frequency differences between cases and controls due to systematic ancestry differences-can cause spurious associations in disease studies. We describe a method that enables explicit detection and correction of population stratification on a genome-wide scale. Our method uses principal components analysis to explicitly model ancestry differences between cases and controls. The resulting correction is specific to a candidate marker's variation in frequency across ancestral populations, minimizing spurious associations while maximizing power to detect true associations. Our simple, efficient approach can easily be applied to disease studies with hundreds of thousands of markers.
            Article 0 comments Cited 1305 times – based on 0 reviews     Review now
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              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              METAL: fast and efficient meta-analysis of genomewide association scans

              Cristen Willer, Yun Li, Gonçalo R Abecasis (2010)
              Summary: METAL provides a computationally efficient tool for meta-analysis of genome-wide association scans, which is a commonly used approach for improving power complex traits gene mapping studies. METAL provides a rich scripting interface and implements efficient memory management to allow analyses of very large data sets and to support a variety of input file formats. Availability and implementation: METAL, including source code, documentation, examples, and executables, is available at http://www.sph.umich.edu/csg/abecasis/metal/ Contact: goncalo@umich.edu
              Article 0 comments Cited 1206 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: 14 November 2013
                Publication date (Electronic): 06 October 2013
                Publication date (Print): November 2013
                Publication date PMC-release: 01 May 2014
                Volume: 45
                Issue: 11
                Electronic Location Identifier: 10.1038/ng.2797
                Affiliations
                [1 ]Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA
                [2 ]Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan 48109, USA
                [3 ]Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109, USA
                [4 ]Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan 48109, USA
                [5 ]Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts 02118, USA
                [6 ]Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
                [7 ]Broad Institute, Program in Medical and Population Genetics, Cambridge, Massachusetts 02142, USA
                [8 ]Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden
                [9 ]Science for Life Laboratory, Uppsala University, Uppsala, Sweden
                [10 ]Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, CB10 1SA, Hinxton, United Kingdom
                [11 ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
                [12 ]Department of Genetics, University of North Carolina, Chapel Hill, NC 27599 USA
                [13 ]Division of Preventive Medicine, Brigham and Women’s Hospital, 900 Commonwealth Ave., Boston MA 02215, USA
                [14 ]Harvard Medical School, Boston MA 02115, USA
                [15 ]Service of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland
                [16 ]Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
                [17 ]Division of Preventive Medicine and Health Services Research, Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
                [18 ]Genetic Epidemiology Unit, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands
                [19 ]Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
                [20 ]Medical Research Institute, University of Dundee, Ninewells Hospital and Medical School. Dundee, DD1 9SY, United Kingdom
                [21 ]Cardiology, Department of Specialities of Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland
                [22 ]Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
                [23 ]Estonian Genome Center of the University of Tartu, Tartu, Estonia
                [24 ]Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
                [25 ]Department of Genetics, Washington University School of Medicine, USA
                [26 ]Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom
                [27 ]Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, Scotland, United Kingdom
                [28 ]Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
                [29 ]Hjelt Institute, Department of Public Health, University of Helsinki, Finland
                [30 ]Centre For Paediatric Epidemiology and Biostatistics/MRC Centre of Epidemiology for Child Health, University College of London Institute of Child Health, London, United Kingdom
                [31 ]Centre for Medical Systems Biology, Leiden, the Netherlands
                [32 ]Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
                [33 ]Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden
                [34 ]Genome Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
                [35 ]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
                [36 ]Biocenter Oulu, University of Oulu, Oulu, Finland
                [37 ]Institute of Health Sciences, University of Oulu, Finland
                [38 ]Institute for Molecular Medicine Finland FIMM, University of Helsinki, Finland
                [39 ]Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland
                [40 ]Department of Internal Medicine II – Cardiology, University of Ulm Medical Centre, Ulm, Germany
                [41 ]Mannheim Institute of Public Health, Social and Preventive Medicine, Medical Faculty of Mannheim, University of Heidelberg, Ludolf-Krehl-Strasse 7-11, 68167 Mannheim, Germany
                [42 ]Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
                [43 ]MRC Epidemiology Unit, Institute of Metabolic Science, Box 285, Addenbrooke’s Hospital, Hills Road, Cambridge, CB2 0QQ, United Kingdom
                [44 ]Department of Clinical Chemistry, Fimlab Laboratories, Tampere 33520, Finland
                [45 ]Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33014, Finland
                [46 ]Department of Twin Research and Genetic Epidemiology, King’s College London, London, United Kingdom
                [47 ]Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland, School of Medicine, Baltimore, Maryland
                [48 ]Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany
                [49 ]Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians University, Munich, Germany
                [50 ]Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University of Munich, Munich, Germany
                [51 ]Department of Epidemiology, University of Groningen, University Medical Center Groningen, The Netherlands
                [52 ]Division of Endocrinology, Children’s Hospital Boston, Massachusetts 02115, USA
                [53 ]Division of Genetics, Program in Genomics, Children’s Hospital, Boston, Massachusetts 02115, USA
                [54 ]Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, 09042, Italy
                [55 ]Massachusetts General Hospital/Broad Institute, Harvard University, Cambridge, MA, USA
                [56 ]Center for Neurobehavioral Genetics, The Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, USA
                [57 ]Genetic Epidemiology Group, Deparment of Epidemiology and Public Health, UCL, London WC1E 6BT, United Kingdom
                [58 ]Department of Clinical Sciences, Genetic & Molecular Epidemiology Unit, Lund University Diabetes Center, Scania University Hosptial, Malmö, Sweden
                [59 ]Department of Odontology, Umeå University, Umeå, Sweden
                [60 ]Department of Public Health and Primary Care, Unit of Medicine, Umeå University, Umeå, Sweden
                [61 ]Dipartimento di Scienze Biomediche, Universita di Sassari, 07100 SS, Italy
                [62 ]Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
                [63 ]Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden
                [64 ]Clinical Research Branch, National Institute Health, Baltimore, MD, USA
                [65 ]deCODE Genetics/Amgen, 101 Reykjavik, Iceland
                [66 ]Department of Genetics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA
                [67 ]Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania - School of Medicine, Philadelphia PA, 19104, USA
                [68 ]Human Genetics Center, University of Texas Health Science Center - School of Public Health, Houston, TX 77030, USA
                [69 ]HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA
                [70 ]MRC Unit for Lifelong Health and Ageing, 33 Bedford Place, London, WC1B 5JU, United Kingdom
                [71 ]Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
                [72 ]Ealing Hospital, Southall, Middlesex UB1 3HW, United Kingdom
                [73 ]MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda
                [74 ]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
                [75 ]Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
                [76 ]Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA
                [77 ]Department of Experimental Medicine, University of Milano Bicocca, Italy
                [78 ]MedStar Health Research Institute, 6525 Belcrest Road, Suite 700, Hyattsville, MD 20782, USA
                [79 ]Research Centre on Public Health, University of Milano Bicocca, Italy
                [80 ]Department of Dietetics-Nutrition, Harokopio University, 70 El. Venizelou Str, Athens, Greece
                [81 ]Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg 85764, Germany
                [82 ]Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg 85764, Germany
                [83 ]Department of Epidemiology and Biostatistics, MRC Health Protection Agency (HPA) Centre for Environment and Health, School of Public Health, Imperial College London, UK
                [84 ]The Laboratory in Mjodd, 108 Reykjavik, Iceland
                [85 ]Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
                [86 ]Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
                [87 ]Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg 85764, Germany
                [88 ]Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, OX3 7LJ, United Kingdom
                [89 ]Department of Public Health and Clinical Medicine, Nutritional research, Umeå University, Umeå, Sweden
                [90 ]Department of Clinical Sciences/Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland
                [91 ]MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, United Kingdom
                [92 ]Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD 20892, USA
                [93 ]Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy - Affiliated Institute of the University of Lübeck, Lübeck, Germany
                [94 ]Division of Endocrinology & Metabolism, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
                [95 ]Hannover Unified Biobank, Hannover Medical School, Hannover 30625, Germany
                [96 ]Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
                [97 ]Clinical Gerontology Unit, University of Cambridge, Cambridge, United Kingdom
                [98 ]Kuopio Research Institute of Exercise Medicine, Kuopio, Finland
                [99 ]Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, School of Medicine, National Yang-Ming University, Taipei, Taiwan
                [100 ]Diabetes Prevention Unit, National Institute for Health and Welfare, 00271 Helsinki, Finland
                [101 ]The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, USA
                [102 ]The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at ount Sinai, New York, USA
                [103 ]The Mindich Child Health and Development Institute, The Icahn School of Medicine at Mount Sinai, New York
                [104 ]School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, United Kingdom
                [105 ]Institute for Medical Informatics and Biometrics, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany
                [106 ]Laboratory of Genetics, National Institute on Aging, Baltimore, MD21224, USA
                [107 ]Department of Clinical Pharmacology, University of Tampere School of Medicine, Tamperew 33014, Finland
                [108 ]Department of Internal Medicine, Päijät-Häme Central Hospital, Lahti, Finland
                [109 ]Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland
                [110 ]Department of Clinical Biochemistry, Landspitali University Hospital, 101 Reykjavik, Iceland
                [111 ]Department of Medical Genetics, Haartman Institute, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
                [112 ]Genetic Epidemiology Group, Wellcome Trust Sanger Institute, Hinxton, Cambridge, United ingdom
                [113 ]Department of Statistical Sciences, University College of London, London, United Kingdom
                [114 ]National Institute for Health and Welfare, Oulu, Finland
                [115 ]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
                [116 ]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
                [117 ]Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
                [118 ]Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
                [119 ]Netherlands Genomics Initiative (NGI)-sponsored Netherlands Consortium for Healthy Aging NCHA), Leiden, The Netherlands
                [120 ]Department of Clinical Sciences/Clinical Chemistry, University of Oulu, Oulu, Finland
                [121 ]National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester LE3 9QP, UK
                [122 ]Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, UK
                [123 ]Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria
                [124 ]School of International Development, University of East Anglia, Norwich NR4 7TJ, United Kingdom
                [125 ]University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland
                [126 ]INSERM UMRS 937, Pierre and Marie Curie University, Paris, France
                [127 ]Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, The Netherlands
                [128 ]LifeLines Cohort Study, University of Groningen, University Medical Center Groningen, The Netherlands
                [129 ]Department of Genetics, University of Groningen, University Medical Center Groningen, The Netherlands
                [130 ]Department of Biological Psychology, VU Univ, Amsterdam, The Netherlands
                [131 ]Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway
                [132 ]Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA
                [133 ]Department of Epidemiology and Public Health, EA 3430, University of Strasbourg, Faculty of Medicine, Strasbourg, France
                [134 ]Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
                [135 ]Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy
                [136 ]Chemical Pathology, Department of Pathology, University of the West Indies, Mona, Kingston 7, Jamaica
                [137 ]Institute of Social and Preventive Medicine (IUMSP), Lausanne University Hospital, Route de la Corniche 10, 1010 Lausanne, Switzerland
                [138 ]Division of Endocrinology and Diabetes, Department of Internal Medicine, Ulm University Medical Centre, Ulm, Germany
                [139 ]Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore
                [140 ]Department of Medicine III, University of Dresden, Medical Faculty Carl Gustav Carus, Fetscherstrasse 74, 01307 Dresden, Germany
                [141 ]Ministry of Health, Victoria, Republic of Seychelles
                [142 ]Service of Nephrology, Lausanne University Hospital, Lausanne, Switzerland
                [143 ]Imperial College Healthcare NHS Trust, London, United Kingdom
                [144 ]Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, California, USA
                [145 ]Department of Medicine, University of California Los Angeles, Los Angeles, California, USA
                [146 ]Department of Preventive Medicine and Epidemiology, Loyola University Medical School, Maywood, Illinois 60153, USA
                [147 ]Office of Population Studies Foundation, University of San Carlos, Talamban, Cebu City, Philippines
                [148 ]Department of Cardiology, Toulouse University School of Medicine, Rangueil Hospital, Toulouse, France
                [149 ]Department of Psychiatry, University of California, Los Angeles, USA
                [150 ]Department of Clinical Sciences, Lund University, SE-20502, Malmö, Sweden
                [151 ]Department of Medicine, Helsinki University Hospital, FI-00029 Helsinki, Finland
                [152 ]Icelandic Heart Association, Kopavogur, Iceland
                [153 ]Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
                [154 ]Laboratory of Epidemiology, Demography, and Biometry, National Institute on Ageing, Bethesda, MD, USA
                [155 ]Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan
                [156 ]Cardiovascular Genetics, BHF Laboratories, Institute Cardiovascular Science, University College London, London, United Kingdom
                [157 ]Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA
                [158 ]HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway
                [159 ]Kaiser Permanente, Division of Research, Oakland, CA, USA
                [160 ]Unit of Primary Care, Oulu University Hospital, Oulu, Finland
                [161 ]Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland
                [162 ]Department of Clinical Physiology, University of Tampere School of Medicine, Tampere 33014, Finland
                [163 ]Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland
                [164 ]Institute of Clinical Medicine, Department of Medicine, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, Finland
                [165 ]National Heart & Lung Institute, Imperial College London, Hammersmith Hospital, London, United Kingdom
                [166 ]Children’s Hospital Oakland Research Institute, 5700 Martin Luther King Junior Way, Oakland, CA 94609, USA
                [167 ]Department of Medicine, University of Eastern Finland and Kuopio University Hospital, 70210 Kuopio, Finland
                [168 ]Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark
                [169 ]Odense Patient data Explorative Network (OPEN), Odense University Hospital, Odense, Denmark
                [170 ]Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Finland
                [171 ]Department of Medical Sciences, Uppsala University, Uppsala, Sweden
                [172 ]Queensland Institute of Medical Research, Locked Bag 2000, Royal Brisbane Hospital, Queensland 4029, Australia
                [173 ]Synlab Academy, Synlab Services GmbH,Gottlieb-Daimler-Straße 25, 68165 Mannheim, Germany
                [174 ]Tropical Metabolism Research Unit, Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston 7, Jamaica
                [175 ]U872 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, 75006 Paris, France
                [176 ]Department of Medicine, Kuopio University Hospital, Kuopio, Finland
                [177 ]Department of Neurology, General Central Hospital, Bolzano, Italy
                [178 ]Department of Neurology, University of Lübeck, Lübeck, Germany
                [179 ]Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA
                [180 ]Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA
                [181 ]Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland
                [182 ]Center for Non-Communicable Diseases, Karachi, Pakistan
                [183 ]Department of Medicine, University of Pennsylvania, USA
                [184 ]Unit of Chronic Disease Epidemiology and Prevention, National Institute for Health and Welfare, Helsinki, Finland
                [185 ]South Karelia Central Hospital, Lappeenranta, Finland
                [186 ]Paul Langerhans Institute Dresden, German Center for Diabetes Research (DZD), Dresden, Germany
                [187 ]Division of Endocrine and Metabolism, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
                [188 ]Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, Maryland
                [189 ]Faculty of Medicine, University of Iceland, 101 Reykjavík, Iceland
                [190 ]Division of Population Health Sciences and Education, St George’s, University of London, Cranmer Terrace, London SW17 0RE, United Kingdom
                [191 ]Department of Pharmacological Sciences, University of Milan, Monzino Cardiology Center, IRCCS, Milan, Italy
                [192 ]Centre for Vascular Prevention, Danube-University Krems, 3500 Krems, Austria
                [193 ]King Abdulaziz University, Faculty of Medicine, Jeddah 21589, Saudi Arabia
                [194 ]Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, 28046
                [195 ]Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Finland
                [196 ]Research Unit, Kuopio University Hospital, Kuopio, Finland
                [197 ]Department of Medicine, Lausanne University Hospital, Switzerland
                [198 ]Department of Endocrinology, University of Groningen, University Medical Center Groningen, The Netherlands
                [199 ]Department of Cardiovascular Epidemiology and Population Genetics, National Center for rdiovascular Investigation, Madrid, Spain
                [200 ]IMDEA-Alimentacion, Madrid, Spain
                [201 ]Nutrition and Genomics Laboratory, Jean Mayer-USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA
                [202 ]Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
                [203 ]Framingham Heart Study, Framingham, MA, USA
                [204 ]Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, USA
                [205 ]Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
                [206 ]Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
                Author notes
                [† ]Correspondence To: Cristen Willer, Division of Cardiovascular Medicine and Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI, cristen@ 123456umich.edu ; Karen Mohlke, Department of Genetics, University of North Carolina Medical School, Chapel Hill, NC, mohlke@ 123456med.unc.edu ; Erik Ingelsson, Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden, erik.ingelsson@ 123456medsci.uu.se ; Gonçalo Abecasis, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, goncalo@ 123456umich.edu
                Article
                Manuscript ID: NIHMS524703
                DOI: 10.1038/ng.2797
                PMC ID: 3838666
                PubMed ID: 24097068
                SO-VID: e20d45a9-0666-4804-b93d-15d9baa59a20
                License:

                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 HL109946 || HL
                Funded by: National Heart, Lung, and Blood Institute : NHLBI
                Award ID: R00 HL094535 || HL
                Categories
                Subject: Article

                ScienceOpen disciplines: Genetics
                Data availability:
                ScienceOpen disciplines: Genetics

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