© 2010 Nature America, Inc. All rights reserved. A A full list of authors and affiliations appear at the end of the paper. descent We Genome-wide RESULTS with adjustment genome-wide (GIANT) distinct ing associated wide maintenance genetic sition 22%–61% tion ­adiposity. by hypertension more metabolic as measured from 2 ­circumference Central strong These dimorphism, and TBX15-WARS2 up of adiposity. Waist-hip genetic waist-hip Meta-analysis Nature Ge Nature Received 6 May; accepted 15 September; published online 10 October 2010;

diabetes

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­ © 2010 Nature America, Inc. All rights reserved. rs9491696 S T β SSPN loci effect-size significance wide of (34,601 in associated effects variance Given Sexual based from distribution. null the under statistic test the around CI 95% the represents area gray The (green). associations significant 14 the or (blue) signal reported recently the either of 1 Mb within SNPs removing after and (black) WHR of meta-analysis discovery the for SNPs of plot quantile ( (green). significance genome-wide achieve not did stage follow-up the in tested GWAScombining meta-analysis data with Twothat from (orange). studies the follow-up loci ( association y (with in studies of shows discovery results the meta-analysis WHR association 1 Figure s e l c i t r A  rs6905288 rs984222 rs1055144 rs10195252 rs4846567 rs1011731 rs718314 rs1294421 rs1443512 rs6795735 rs4823006 rs6784615 rs6861681 a meta-analysis. Details onbetween-studyheterogeneityaregiven in up samplesshowedgenome-widesignificant results( studies (upto77,167subjects),follow-up studies(upto113,636subjects)andbothcombined (upto190,781subjects).Fourteenofthe sixteenSNPsexaminedinthefollow- P rs7081678 rs2076529 Further EA, effectallele(WHR-increasing alleleontheforwardstrand). a axis and the on SNP position genomic the valuesand able able 1 NPs evaluatedinfollowupachievinggenome-widesignificance

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© 2010 Nature America, Inc. All rights reserved. diamond and plotted using the the using plotted and diamond –log (with loci 14 for studies 2 Figure ciated (4.1 LYPLAL1 association). Nature Ge Nature (pairwise SNP index the with LD reflect to colored –log P –log10 P –log10 P –log10 P –log10 P 10 10 10 10 10 10 15 15 15 20 30 40 20 25 0 0 2 4 6 8 0 5 0 5 0 5

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TBX15-WARS2 axis and the SNP genomic position on the the on position genomic SNP the and axis of Recombination rate (cM/Mb) rate Recombination Recombination rate (cM/Mb) rate Recombination ) (cM/Mb rate Recombination Recombination rate Recombination r

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© 2010 Nature America, Inc. All rights reserved. to array ­investigation. tribution, of central effects of different ­adipocyte-specific distribution. including and genes for regions look tions ferences based the that presumed 6 of peripheral ADAMTS9 in study previously-reported in lower Grb14 inferences this triglyceride able candidate loci. and from interest. terize phenotype, such risk with ence contribution ings, buted ­differences clear tion at BMI Nature Ge Nature to

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120315, Funding Note: of Methods M URLs. for ­beneficial implement, tion tackle population bution fied derived of clinical ­proportion Education Pomerania, Health; Research Knut Medical and (JDRF); Juho Henriksen University and Medical 01GS0823); National fuer Health pour Finnish of Research West 01ZZ0103, Fellowship); LSHG-CT-2004-518153, LSHG-CT-2004-512066, 01643, 245536, Government Medical Grant, Donald Research Health; Assessment; Contrat Research Medical Research; (DK46200); Biomedicum AB; ALF/LUA Fellowship 130326, 129680, Acknowledgments

Cardiovascular ethods the these

future Alice Korsholm; Augustinus Forschung

Vainio le to Pomerania; Krohn, Supplementary of

Med

QLG2-CT-2002-01254,

in

paper

Développement

overall Ministry Danish

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Ministry

129269, DG 209072, 129494, Plan Karolinska

LocusZoom, Genomics Society; Center Research characterize and

overall

for

Genome

(IZKF), Society; Council; Centre;

perspective, Finland;

Wallenberg British

from

Gothenburg; variants

and

and Central Foundation; Reynolds grant; 01ZZ0403,

Germany;

Drive; German

Foundation; British drug patterns this XII,

Danish Federal

Microarray

SF0180142s08; Etat

Helsinki

related of

differences

and at

Sport

Healthway,

Heart

und any and

Foundation;

117797, 210595, 10404,

study obesity

genetic

HEALTH-F4-2007-201413, Gyllenberg of

Heart Finnish of

CamStrad; detailed http://www.nature.com/naturegenetics/.

Affymetrix,

University

Région energy Finnish Foundation;

Research;

Research

DIAB GEN-AU

EMGO+ discovery. Hospital;

for

Diabetes Cultural

Institute

Education;

the

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Ministry information Research of Foundation; to

Foundation;

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121584, 213225 Core

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de Diabetes

fat through Foundation variance

provided Western balance

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institute;

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Finnish

France;

imaging

Affairs Hjartavernd Foundation; and ‘GOLD’ European of Chief Association causal

Tyrol Becket

University,

distribution Association; (B27);

Inc.,

of

95201408

(German

Facility Council

Cambridge LSHG-CT-2006-018947,

Leipzig, patterns Folkhälsan

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© 2010 Nature America, Inc. All rights reserved. Boston, Massachusetts, Boston, USA. Massachusetts, 51 Queensland Institute of Medical Research, Queensland, Australia. Montréal, Montreal, Quebec, Canada. 45 related traits Consortium) investigators. Medicine, St. Louis, Missouri, USA. 39 Merck Laboratories, & Co., Inc., Boston, USA. Massachusetts, Genetics, Leiden University Medical Center, Leiden, The Netherlands. School of Public Health, Boston, USA. Massachusetts, 31 Science and Innovation Campus, Oxfordshire, UK. Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. Lausanne, Switzerland. Biocenter, Tartu, Estonia. and Endocrinology Program in Genomics, Children’s Hospital, Boston, USA. Massachusetts, 19 Nature Ge Nature Institute Institute of Human Nuthetal, Nutrition Germany.Potsdam-Rehbruecke, Greifswald, Germany. del Neurofarmacologia CNR, Monserrato, Cagliari, Italy. 78 and Endocrinology Metabolism, University of Oxford, Oxford, UK. USA. Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria. 71 Queen Mary University of London, London UK. 68 67 66 University Amsterdam, Amsterdam, The Netherlands. 63 Seattle, Washington, USA. London, UK. Biotechnology, Huntsville, Alabama, USA. Cambridge, USA. Massachusetts, Laboratory, Queensland Institute of Medical Research, Queensland, Australia. Gentofte, Gentofte, Denmark. Center, Leiden, The Netherlands. 144 The Netherlands. 142 140 Leicester, UK. 137 135 Public Health, University of Helsinki, Helsinki, Finland. 132 Dublin, Ireland. Children (ALSPAC) Laboratory, Department of Social Medicine, University of Bristol, Bristol, UK. 127 La Riche, France. University of Science and Technology, Levanger, Norway. University Hospital, Kuopio, Finland. Germany. Finland. Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland. Institute for Health and Welfare, Department of Chronic Disease Prevention, Population Studies Unit, Turku, Finland. Australia, Australia. Lübeck, Lübeck, Germany). Kuopio, Kuopio, Finland. 110 109 Pathobiochemistry, University of Dresden, Dresden, Germany. Los Angeles, California, USA. 103 Helsinki, Finland. Protection Agency (HPA) Centre for Environment and Health, London, UK. Edinburgh, Teviot Place, Edinburgh, Scotland, UK. of Endocrinology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. Sweden. Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. 90 University of Southern California, Los Angeles, California, USA. Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. 86 84 The Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts, USA. National Institute for Health and Welfare, Department of Chronic Disease Prevention, Unit of Public Health Genomics, Helsinki, Finland. Department Department of Primary Industries, Melbourne, Victoria, Australia. Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, Oxford, UK. General Massachusetts Hospital (MGH) Weight Center, General Massachusetts Hospital, Boston, USA. Massachusetts, Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK. Centre Centre for Genetic Epidemiology and University Biostatistics, of Western Australia, Crawley, Western Australia, Australia. MRC Centre for Causal Analyses in Translational Epidemiology, Department of Social Medicine, Oakfield House, Bristol, UK. Hagedorn Research Institute, Gentofte, Denmark. Department of Medicine, Stanford University School of Medicine, Stanford, California, USA. Clinical Pharmacology and Barts and The London Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary, University of London, London, UK. Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. Department of Neurology, Boston University School of Medicine, Boston, USA. Massachusetts, Department Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. Department of voor Psychiatry/Instituut Extramuraal Geneeskundig Onderzoek (EMGO) Institute, VU University Medical Center, Amsterdam, South Karelia Central Hospital, Finland. Lappeenranta, Department of Clinical Sciences, Lund University, Malmö, Sweden. Department of Medicine, Levanger Hospital, The Nord-Trøndelag Health Trust, Levanger, Norway. Department of Medicine, Cardiovascular University of Oxford, John Radcliffe Hospital, Headington, Oxford, UK. Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK. Institute Institute of Biomedicine, Department of Physiology, University of Oulu, Oulu, Finland. National Institute for Health and Welfare, Department of Chronic Disease Prevention, Chronic Disease Epidemiology and Prevention Unit, Helsinki, Finland. Folkhalsan Research Centre, Helsinki, Finland. 74 Andrija Andrija Stampar School of Public Health, Medical School, University of Zagreb, Zagreb, Croatia. 118 94 120 Zentrum Zentrum für Zahn-, Mund- und Greifswald, Germany.Kieferheilkunde, Interdisciplinary Centre Interdisciplinary for Clinical Research, University of Leipzig, Leipzig, Germany. Croatian Croatian Centre for Global Health, School of Medicine, University of Split, Split, Croatia. 60 n 139 etics Department Department of Medicine, University of Washington, Seattle, Washington, USA. 130 143 Leicester Leicester National Institute for Health Research (NIHR) Biomedical Research Unit in Disease, Cardiovascular Glenfield Hospital, Leicester, UK. 125 101 Department Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada. 148 114 Atherosclerosis Research Atherosclerosis Unit, Department of Medicine, Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. Centre Centre National de Genotypage, Evry, Paris, France. National National Institute for Health and Welfare, Helsinki, Finland. 81

Department Department of Physiatrics, Lapland Central Hospital, Rovaniemi, Finland. Busselton Busselton Population Medical Research Foundation Inc., Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia. 25 National National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA. ADVANCE ONLINE PUBLICATION ONLINE ADVANCE 112 23 Swiss Swiss Institute of Lausanne, Bioinformatics, Switzerland. 62 Institute Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia. 113 Institute Institute of Genetic Medicine, European Academy (EURAC), Bozen-Bolzano Italy Bolzano-Bozen, (affiliated Institute of the University of MRC MRC Human Genetics Unit, Institute for Genetics and Molecular Medicine, Western General Hospital, Edinburgh, Scotland, UK. 106 53 PathWest Laboratory of Western Australia, Department of Molecular Genetics, J Block, QEII Medical Centre, Nedlands, Western Icelandic Icelandic Heart Association, Kopavogur, Iceland. Department Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. 146 57 Department Department of Molecular Biology, General Massachusetts Hospital, Boston, USA. Massachusetts, 41 Institut Institut für Klinische Chemie und Universität Greifswald, Greifswald, Germany.Laboratoriumsmedizin, 122 48 Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK. 43 Department Department of Twin Research and Genetic Epidemiology, King’s College London, London, UK. Nord-Trøndelag Health Study (HUNT) Research Centre, Department of Public Health and General Practice, Norwegian Department Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands. 59 Department Department of Epidemiology and School Biostatistics, of Public Health, Faculty of Medicine, Imperial College London, 69 Institute Institute of Health Sciences, University of Oulu, Oulu, Finland. 29 104 98 Department of Statistics, University of Oxford, Oxford, UK. 85 Department Department of Internal Medicine B, University,Ernst-Moritz-Arndt Greifswald, Germany. Vasa Central Hospital, Vasa, Finland. 65 Regensburg Regensburg University Medical Center, Clinic and Policlinic for Internal Medicine II, Regensburg, Germany. 33 80 Department Department of Genetics and Pathology, Rudbeck Laboratory, University of Uppsala, Uppsala, Sweden. 134 123 Department Department of Harvard Biostatistics, School of Public Health, Boston, USA. Massachusetts, 27 Interfaculty Interfaculty Institute for Genetics Greifswald, and Functional Genomics, Ernst-Moritz-Arndt-University 141 Obesity Obesity Research Unit, Department of Psychiatry, Helsinki University Central Hospital, Helsinki, Finland. Department Department of Pharmacy and Pharmacology, University of Bath, Bath, UK. Finnish Finnish Institute of Occupational Health, Oulu, Finland. Division Division of Cardiology, Laboratory,Cardiovascular Helsinki University Central Hospital, Helsinki, Finland. 108

37 89 Pacific Pacific Biosciences, Menlo Park, California, USA. Department Department of and Clinical Sciences/Obstetrics Gynecology, University of Oulu, Oulu, Finland. 77 50 Division Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, USA. Massachusetts, Institute Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland. Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. 46 Montreal Montreal Heart Institute, Montreal, Quebec, Canada. 35 138 93 83 National National Heart and Lung Institute, Imperial College London, London, UK. Lund Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Malmö, 126 Department Department of Sciences, Cardiovascular University of Leicester, Glenfield Hospital, Department Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA. 100 Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland. Department Department of General Practice and Primary Health Care, University of Helsinki, 56 Program Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, 54 95 117 102 University University of Iceland, Reykjavik, Iceland. Department Department of Medicine III, University of Dresden, Dresden, Germany. 26 National National Institute for Health and Welfare, Diabetes Prevention Unit, Helsinki, Helsinki Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland. Department Department of Epidemiology, School of Public Health, University of North 73 111 Department Department of University Biostatistics, of Washington, Seattle, Washington, 105 21 Department Department of Psychiatry, Kuopio University Hospital and University of 61 Estonian Estonian Genome Center, University of Tartu, Tartu, Estonia. Center Center for Genetics, Neurobehavioral University of California, 72 Cardiovascular Health Cardiovascular Research Unit, University of Washington, 145 Division Division of Genetic Epidemiology, Department of Medical Genetics, 129 64 42 149 119 Department Department of Biological Psychology, Vrije Universiteit (VU) On On behalf of the MAGIC of (Meta-Analyses Glucose and Insulin- Center Center of Medical Systems Biology, Leiden University Medical Division Division of Health, Research Board, An Bord Taighde Sláinte, 136 School School of Pathology and Laboratory Medicine, University of 40 92 Institut Institut für Universität Pharmakologie, Greifswald, Greifswald, 121 88 24 Department Department of Genetics, Washington University School of National National Institute for Health and Welfare, Oulu, Finland. Department Department of Internal Medicine, Institute of Medicine, Department Department of Preventive Medicine, Keck School of Medicine, Department Department of Medical Genetics, University of Lausanne, 75 Department Department of Medicine, University of Kuopio and Kuopio Gen-Info Gen-Info Ltd, Zagreb, Croatia. 97 Centre Centre for Population Health Sciences, University of 30 Harvard Medical School, Boston, Massachusetts, USA. 70 52 Biocenter Biocenter Oulu, University of Oulu, Oulu, Finland. 38 133 44 Department of Psychiatry, Harvard Medical School, 124 Sage Sage Bionetworks, Seattle, Washington, USA. University University of Melbourne, Parkville, Australia. 116 Finnish Finnish Twin Cohort Study, Department of 128 Institut Institut inter-regional pour la sante (IRSA), 131 32 Hospital Hospital for Children and Adolescents, Avon Longitudinal Study of Parents and 91 Department Department of Epidemiology, Harvard Amgen, Amgen, Cambridge, USA. Massachusetts, 47 Department Department of Physiology, Institute of 55 Department Department of Medicine, Université de 82 87 Queensland Queensland Statistical Genetics Department Department of Epidemiology, German 20 Department Department of Physiology and 107 Divisions Divisions of Genetics and Department Department of Medicine III, 58 49 28 Hudson Hudson Alpha Institute for Neurogenetics Laboratory,Neurogenetics 76 MRC MRC Harwell, Harwell 79 Oxford Oxford Centre for Diabetes, 147 Istituto di Neurogenetica e 99 Steno Steno Diabetes Center,

MRC-Health MRC-Health s e l c i t r A 36 Merck Merck Research 34 115 Human Human National National 96 22

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© 2010 Nature America, Inc. All rights reserved. ([email protected]). addressed to C.M.L. ([email protected]), K.L.M. ([email protected]), C.S.F. ([email protected]), M.I.M. ([email protected]) or I.M.H. Framingham, USA. Massachusetts, Metabolic Science Addenbrooke’s Hospital, Cambridge, UK. Epidemiology, Munich, Germany. School, Boston, USA. Massachusetts, Baltimore, Maryland, USA. Chapel Hill, North Carolina, USA. Einstein College of Medicine, Bronx, New York, USA. USA. VaudoisUniversitaire (CHUV) University Hospital, Lausanne, Switzerland. Molecular Medicine, Uppsala, Sweden. Education Clinical Center, Baltimore Veterans Medical Administration Center, Baltimore, Maryland, USA. University of Washington, Seattle, Washington, USA. Central Hospital, Bolzano, Italy. Leiden, The Netherlands. Helsinki, Finland. USA. Francisco, San Francisco, California, USA. of Research, Kaiser Permanente Northern California, Oakland, California, USA. Lausanne, Lausanne, Switzerland. Studies Coordinating Center, Seattle, Washington, USA. Institute, Department of Public Health, University of Helsinki, Helsinki, Finland. Medicine, Helsinki University Central Hospital, Helsinki, Finland. University of Aarhus, Aarhus, Denmark. Health, Environmental Neuherberg, Germany. der Isar der Technischen Universität München, Munich, Germany. Paris, Paris, France. Hospital, Oxford, UK. Hospital, Glostrup, Denmark. Regensburg, Germany. 166 Common Disease, School of Public Health, Imperial College London, London, UK. 162 160 Turku and Turku University Hospital, Turku, Finland. University of Leipzig, Leipzig, Germany. Germany. Turku, Finland. University of Tampere and Tampere University Hospital, Tampere, Finland. Australia. Western Australia, Nedlands, Western Australia, Australia. s e l c i t r A 1 2

University Paris Sud 11, Unité Mixte de Recherche en Santé (UMRS) 1018, Villejuif, France. Klinik Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Regensburg, Germany. The London School of Hygiene and Tropical Medicine, London, UK. 202 189 Medical Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. National Institute for Health and Welfare, Department of Mental Health and Substance Abuse Services, Unit for Child and Adolescent Mental Health, 156 151 Leipziger Interdisziplinärer Forschungskomplex zu Forschungskomplex Leipziger Interdisziplinärer molekularen Ursachen umwelt- und Erkrankungen (LIFE) Study lebensstilassoziierter Centre, Department Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, Finland. 154 190 The The Department of Clinical Physiology, Turku University Hospital, Turku, Finland. 173 Department Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands. 172 168 185 Cardiovascular Genetics Cardiovascular Research Unit, Université Henri 1, Poincaré-Nancy Nancy, France. Department Department of Endocrinology, Diabetology and Nutrition, Bernard Bichat-Claude University Hospital, Assistance Publique des Hôpitaux de 192 Department Department of Social Services and Health Care, Jakobstad, Finland. Human Human Genetics Center and Institute of Molecular Medicine, University of Texas Health Science Center, Houston, Texas, USA. 207 Department Department of Psychiatry, University Medical Centre Groningen, Groningen, The Netherlands. 170 Division Division of Community Health Sciences, St George’s, University of London, London, UK. 194 Faculty Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark. 211 205 Department Department of Neurology, University of Lübeck, Lübeck, Germany. 214 Faculty Faculty of Medicine, University of Iceland, Reykjavík, Iceland. Department Department of Medical Genetics, University of Helsinki, Helsinki, Finland. 209 These These authors contributed equally to this work. 199 178 157 Klinikum Klinikum Grosshadern, Munich, Germany. Institut Institut für Community Medicine, Greifswald, Germany. 188 Department Department of Medicine III, Prevention and Care of Diabetes, University of Dresden, Dresden, Germany. Coordination Coordination Centre for Clinical Trials, University of Leipzig, Leipzig, Germany. 176 Department Department of Epidemiology and Medicine, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, Institute Institute of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. 159 196 204 INSERM INSERM Centre de Recherche en et Epidémiologie Santé des Populations (CESP) U1018, Villejuif, France. Group Group Health Research Institute, Group Health, Seattle, Washington, USA. 184 Carolina Carolina Center for Genome Sciences, School of Public Health, University of North Carolina Chapel Hill, 150 Service Service of Medical Genetics, Centre Hospitalier VaudoisUniversitaire (CHUV) University Hospital, 213 School School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Division Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham Heart Study, 180 175 Research Research Program of Molecular Medicine, University of Helsinki, Helsinki, Finland. Institute Institute of Human Genetics, Helmholtz Zentrum Research München-German Center for 163 201 South South Asia Network for Chronic Disease, New Delhi, India. 153 Division Division of WashingtonBiostatistics, University School of Medicine, St. Louis, Missouri, Research Research Centre of Applied and Preventive Medicine, Cardiovascular University of Turku, 187 182 165 Department Department of Epidemiology and University Biostatistics, of California, San 210 South South Ostrobothnia Central Hospital, Seinajoki, Finland. Faculty Faculty of Health Science, University of Southern Denmark, Odense, Denmark. 215 Ludwig-Maximilians-Universität, Institute of Medical Ludwig-Maximilians-Universität, Informatics, Biometry and These These authors jointly directed this work. should Correspondence be 167 169 203 161 Regensburg Regensburg University Medical Center, Innere Medizin II, Research Research Centre for Prevention and Health, Glostrup University 191 200 212 Department Department of Epidemiology and Population Health, Albert Department Department of Social Medicine, University of Bristol, Bristol, UK. 155 Department Department of Psychiatry, Leiden University Medical Centre, Department Department of Internal Medicine, Centre Hospitalier 195 University University of Cambridge Metabolic Research Labs, Institute of Department Department of Medicine, University of Leipzig, Leipzig, a Departments Departments of Epidemiology, Medicine and Health Services, 198 DVANCE ONLINE PUBLICATION ONLINE DVANCE Uppsala Uppsala University, Department of Medical Sciences, 171 206 NIHR NIHR Oxford Biomedical Research Centre, Churchill Laboratory Laboratory of Genetics, National Institute on Aging, 174 Institute Institute of Human Genetics, Klinikum rechts 208 158 Department Department of Genetics, Harvard Medical 193 152 Department Department of Medicine, University of Department Department of Neurology, General Department Department of Clinical Chemistry, 197 164 177 Geriatrics Geriatrics Research and Department Department of Genomics of Faculty Faculty of Health Science, 183

Collaborative Health Collaborative Nature Ge Nature 179 Department Department of

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