Gene-Age Interactions in Blood Pressure Regulation: A Large-Scale Investigation with the CHARGE, Global BPgen, and ICBP Consortia
Identifieur interne : 001687 ( Pmc/Corpus ); précédent : 001686; suivant : 001688Gene-Age Interactions in Blood Pressure Regulation: A Large-Scale Investigation with the CHARGE, Global BPgen, and ICBP Consortia
Auteurs : Jeannette Simino ; Gang Shi ; Joshua C. Bis ; Daniel I. Chasman ; Georg B. Ehret ; Xiangjun Gu ; Xiuqing Guo ; Shih-Jen Hwang ; Eric Sijbrands ; Albert V. Smith ; Germaine C. Verwoert ; Jennifer L. Bragg-Gresham ; Gemma Cadby ; Peng Chen ; Ching-Yu Cheng ; Tanguy Corre ; Rudolf A. De Boer ; Anuj Goel ; Toby Johnson ; Chiea-Chuen Khor ; Carla Lluís-Ganella ; Jian N Luan ; Leo-Pekka Lyytik Inen ; Ilja M. Nolte ; Xueling Sim ; Siim S Ber ; Peter J. Van Der Most ; Niek Verweij ; Jing Hua Zhao ; Najaf Amin ; Eric Boerwinkle ; Claude Bouchard ; Abbas Dehghan ; Gudny Eiriksdottir ; Roberto Elosua ; Oscar H. Franco ; Christian Gieger ; Tamara B. Harris ; Serge Hercberg ; Albert Hofman ; Alan L. James ; Andrew D. Johnson ; Mika K Hönen ; Kay-Tee Khaw ; Zoltan Kutalik ; Martin G. Larson ; Lenore J. Launer ; Guo Li ; Jianjun Liu ; Kiang Liu ; Alanna C. Morrison ; Gerjan Navis ; Rick Twee-Hee Ong ; George J. Papanicolau ; Brenda W. Penninx ; Bruce M. Psaty ; Leslie J. Raffel ; Olli T. Raitakari ; Kenneth Rice ; Fernando Rivadeneira ; Lynda M. Rose ; Serena Sanna ; Robert A. Scott ; David S. Siscovick ; Ronald P. Stolk ; Andre G. Uitterlinden ; Dhananjay Vaidya ; Melanie M. Van Der Klauw ; Ramachandran S. Vasan ; Eranga Nishanthie Vithana ; Uwe Völker ; Henry Völzke ; Hugh Watkins ; Terri L. Young ; Tin Aung ; Murielle Bochud ; Martin Farrall ; Catharina A. Hartman ; Maris Laan ; Edward G. Lakatta ; Terho Lehtim Ki ; Ruth J. F. Loos ; Gavin Lucas ; Pierre Meneton ; Lyle J. Palmer ; Rainer Rettig ; Harold Snieder ; E. Shyong Tai ; Yik-Ying Teo ; Pim Van Der Harst ; Nicholas J. Wareham ; Cisca Wijmenga ; Tien Yin Wong ; Myriam Fornage ; Vilmundur Gudnason ; Daniel Levy ; Walter Palmas ; Paul M. Ridker ; Jerome I. Rotter ; Cornelia M. Van Duijn ; Jacqueline C. M. Witteman ; Aravinda Chakravarti ; Dabeeru C. RaoSource :
- American Journal of Human Genetics [ 0002-9297 ] ; 2014.
Abstract
Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p ≤ 5 × 10−8) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the
Url:
DOI: 10.1016/j.ajhg.2014.05.010
PubMed: 24954895
PubMed Central: 4085636
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Gene-Age Interactions in Blood Pressure Regulation: A Large-Scale Investigation with the CHARGE, Global BPgen, and ICBP Consortia</title><author><name sortKey="Simino, Jeannette" sort="Simino, Jeannette" uniqKey="Simino J" first="Jeannette" last="Simino">Jeannette Simino</name><affiliation><nlm:aff id="aff1">Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA</nlm:aff></affiliation></author><author><name sortKey="Shi, Gang" sort="Shi, Gang" uniqKey="Shi G" first="Gang" last="Shi">Gang Shi</name><affiliation><nlm:aff id="aff1">Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA</nlm:aff></affiliation></author><author><name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua C." last="Bis">Joshua C. Bis</name><affiliation><nlm:aff id="aff2">Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA</nlm:aff></affiliation></author><author><name sortKey="Chasman, Daniel I" sort="Chasman, Daniel I" uniqKey="Chasman D" first="Daniel I." last="Chasman">Daniel I. Chasman</name><affiliation><nlm:aff id="aff3">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02215, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Harvard Medical School, Boston, MA 02115, USA</nlm:aff></affiliation></author><author><name sortKey="Ehret, Georg B" sort="Ehret, Georg B" uniqKey="Ehret G" first="Georg B." last="Ehret">Georg B. Ehret</name><affiliation><nlm:aff id="aff5">Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospitals, Geneva 1211, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Gu, Xiangjun" sort="Gu, Xiangjun" uniqKey="Gu X" first="Xiangjun" last="Gu">Xiangjun Gu</name><affiliation><nlm:aff id="aff7">Research Center for Human Genetics, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Guo, Xiuqing" sort="Guo, Xiuqing" uniqKey="Guo X" first="Xiuqing" last="Guo">Xiuqing Guo</name><affiliation><nlm:aff id="aff8">Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA</nlm:aff></affiliation></author><author><name sortKey="Hwang, Shih Jen" sort="Hwang, Shih Jen" uniqKey="Hwang S" first="Shih-Jen" last="Hwang">Shih-Jen Hwang</name><affiliation><nlm:aff id="aff9">Framingham Heart Study, Framingham, MA 01702, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff10">Center for Population Studies, National Heart, Lung, and Blood Institute, Framingham, MA 01702, USA</nlm:aff></affiliation></author><author><name sortKey="Sijbrands, Eric" sort="Sijbrands, Eric" uniqKey="Sijbrands E" first="Eric" last="Sijbrands">Eric Sijbrands</name><affiliation><nlm:aff id="aff11">Department of Internal Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Smith, Albert V" sort="Smith, Albert V" uniqKey="Smith A" first="Albert V." last="Smith">Albert V. Smith</name><affiliation><nlm:aff id="aff12">Icelandic Heart Association, 201 Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="aff13">Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Verwoert, Germaine C" sort="Verwoert, Germaine C" uniqKey="Verwoert G" first="Germaine C." last="Verwoert">Germaine C. Verwoert</name><affiliation><nlm:aff id="aff11">Department of Internal Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Bragg Gresham, Jennifer L" sort="Bragg Gresham, Jennifer L" uniqKey="Bragg Gresham J" first="Jennifer L." last="Bragg-Gresham">Jennifer L. Bragg-Gresham</name><affiliation><nlm:aff id="aff15">Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA</nlm:aff></affiliation></author><author><name sortKey="Cadby, Gemma" sort="Cadby, Gemma" uniqKey="Cadby G" first="Gemma" last="Cadby">Gemma Cadby</name><affiliation><nlm:aff id="aff16">Centre for Genetic Origins of Health and Disease, University of Western Australia, Nedlands, WA 6009, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff17">Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="aff18">Samuel Lunenfeld Research Institute, Toronto, ON M5T 3L9, Canada</nlm:aff></affiliation></author><author><name sortKey="Chen, Peng" sort="Chen, Peng" uniqKey="Chen P" first="Peng" last="Chen">Peng Chen</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation></author><author><name sortKey="Cheng, Ching Yu" sort="Cheng, Ching Yu" uniqKey="Cheng C" first="Ching-Yu" last="Cheng">Ching-Yu Cheng</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff21">Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff22">Department of Ophthalmology, National University Health System, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff23">Singapore Eye Research Institute, Singapore 168751, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff24">Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore 169857, Singapore</nlm:aff></affiliation></author><author><name sortKey="Corre, Tanguy" sort="Corre, Tanguy" uniqKey="Corre T" first="Tanguy" last="Corre">Tanguy Corre</name><affiliation><nlm:aff id="aff25">Department of Medical Genetics, University of Lausanne, 1005 Lausanne, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="aff26">Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland</nlm:aff></affiliation></author><author><name sortKey="De Boer, Rudolf A" sort="De Boer, Rudolf A" uniqKey="De Boer R" first="Rudolf A." last="De Boer">Rudolf A. De Boer</name><affiliation><nlm:aff id="aff27">Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Goel, Anuj" sort="Goel, Anuj" uniqKey="Goel A" first="Anuj" last="Goel">Anuj Goel</name><affiliation><nlm:aff id="aff28">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff29">Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK</nlm:aff></affiliation></author><author><name sortKey="Johnson, Toby" sort="Johnson, Toby" uniqKey="Johnson T" first="Toby" last="Johnson">Toby Johnson</name><affiliation><nlm:aff id="aff30">Clinical Pharmacology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK</nlm:aff></affiliation></author><author><name sortKey="Khor, Chiea Chuen" sort="Khor, Chiea Chuen" uniqKey="Khor C" first="Chiea-Chuen" last="Khor">Chiea-Chuen Khor</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff21">Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff22">Department of Ophthalmology, National University Health System, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff31">Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff32">Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff33">Department of Paediatrics, National University Health System, Singapore 119074, Singapore</nlm:aff></affiliation></author><author><name sortKey="Lluis Ganella, Carla" sort="Lluis Ganella, Carla" uniqKey="Lluis Ganella C" first="Carla" last="Lluís-Ganella">Carla Lluís-Ganella</name><affiliation><nlm:aff id="aff34">Cardiovascular Epidemiology and Genetics, IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Luan, Jian N" sort="Luan, Jian N" uniqKey="Luan J" first="Jian N" last="Luan">Jian N Luan</name><affiliation><nlm:aff id="aff35">MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK</nlm:aff></affiliation></author><author><name sortKey="Lyytik Inen, Leo Pekka" sort="Lyytik Inen, Leo Pekka" uniqKey="Lyytik Inen L" first="Leo-Pekka" last="Lyytik Inen">Leo-Pekka Lyytik Inen</name><affiliation><nlm:aff id="aff36">Department of Clinical Chemistry, Fimlab Laboratories, Tampere 30101, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="aff37">Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33101, Finland</nlm:aff></affiliation></author><author><name sortKey="Nolte, Ilja M" sort="Nolte, Ilja M" uniqKey="Nolte I" first="Ilja M." last="Nolte">Ilja M. Nolte</name><affiliation><nlm:aff id="aff38">Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Sim, Xueling" sort="Sim, Xueling" uniqKey="Sim X" first="Xueling" last="Sim">Xueling Sim</name><affiliation><nlm:aff id="aff15">Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff39">Centre for Molecular Epidemiology, National University of Singapore, Singapore 119260, Singapore</nlm:aff></affiliation></author><author><name sortKey="S Ber, Siim" sort="S Ber, Siim" uniqKey="S Ber S" first="Siim" last="S Ber">Siim S Ber</name><affiliation><nlm:aff id="aff40">Human Molecular Genetics Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia</nlm:aff></affiliation></author><author><name sortKey="Van Der Most, Peter J" sort="Van Der Most, Peter J" uniqKey="Van Der Most P" first="Peter J." last="Van Der Most">Peter J. Van Der Most</name><affiliation><nlm:aff id="aff38">Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Verweij, Niek" sort="Verweij, Niek" uniqKey="Verweij N" first="Niek" last="Verweij">Niek Verweij</name><affiliation><nlm:aff id="aff27">Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zhao, Jing Hua" sort="Zhao, Jing Hua" uniqKey="Zhao J" first="Jing Hua" last="Zhao">Jing Hua Zhao</name><affiliation><nlm:aff id="aff35">MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK</nlm:aff></affiliation></author><author><name sortKey="Amin, Najaf" sort="Amin, Najaf" uniqKey="Amin N" first="Najaf" last="Amin">Najaf Amin</name><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Boerwinkle, Eric" sort="Boerwinkle, Eric" uniqKey="Boerwinkle E" first="Eric" last="Boerwinkle">Eric Boerwinkle</name><affiliation><nlm:aff id="aff41">Human Genetics Center, University of Texas Health Sciences Center, Houston, TX 77225, USA</nlm:aff></affiliation></author><author><name sortKey="Bouchard, Claude" sort="Bouchard, Claude" uniqKey="Bouchard C" first="Claude" last="Bouchard">Claude Bouchard</name><affiliation><nlm:aff id="aff42">Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA</nlm:aff></affiliation></author><author><name sortKey="Dehghan, Abbas" sort="Dehghan, Abbas" uniqKey="Dehghan A" first="Abbas" last="Dehghan">Abbas Dehghan</name><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Eiriksdottir, Gudny" sort="Eiriksdottir, Gudny" uniqKey="Eiriksdottir G" first="Gudny" last="Eiriksdottir">Gudny Eiriksdottir</name><affiliation><nlm:aff id="aff12">Icelandic Heart Association, 201 Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Elosua, Roberto" sort="Elosua, Roberto" uniqKey="Elosua R" first="Roberto" last="Elosua">Roberto Elosua</name><affiliation><nlm:aff id="aff34">Cardiovascular Epidemiology and Genetics, IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="aff43">Epidemiology and Public Health Network (CIBERESP), 08036 Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Franco, Oscar H" sort="Franco, Oscar H" uniqKey="Franco O" first="Oscar H." last="Franco">Oscar H. Franco</name><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Gieger, Christian" sort="Gieger, Christian" uniqKey="Gieger C" first="Christian" last="Gieger">Christian Gieger</name><affiliation><nlm:aff id="aff44">Institute of Genetic Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B." last="Harris">Tamara B. Harris</name><affiliation><nlm:aff id="aff45">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, NIH, Bethesda, MD 20892, USA</nlm:aff></affiliation></author><author><name sortKey="Hercberg, Serge" sort="Hercberg, Serge" uniqKey="Hercberg S" first="Serge" last="Hercberg">Serge Hercberg</name><affiliation><nlm:aff id="aff46">U557 Institut National de la Santé et de la Recherche Médicale, U1125 Institut National de la Recherche Agronomique, Université Paris 13, 93000 Bobigny, France</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="James, Alan L" sort="James, Alan L" uniqKey="James A" first="Alan L." last="James">Alan L. James</name><affiliation><nlm:aff id="aff47">Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff48">School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA 6009, Australia</nlm:aff></affiliation></author><author><name sortKey="Johnson, Andrew D" sort="Johnson, Andrew D" uniqKey="Johnson A" first="Andrew D." last="Johnson">Andrew D. Johnson</name><affiliation><nlm:aff id="aff9">Framingham Heart Study, Framingham, MA 01702, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff49">Cardiovascular Epidemiology and Human Genomics Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA</nlm:aff></affiliation></author><author><name sortKey="K Honen, Mika" sort="K Honen, Mika" uniqKey="K Honen M" first="Mika" last="K Hönen">Mika K Hönen</name><affiliation><nlm:aff id="aff50">Department of Clinical Physiology, Tampere University Hospital, Tampere 33521, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="aff51">Department of Clinical Physiology, University of Tampere School of Medicine, Tampere 33521, Finland</nlm:aff></affiliation></author><author><name sortKey="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name><affiliation><nlm:aff id="aff52">Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge CB2 2SR, UK</nlm:aff></affiliation></author><author><name sortKey="Kutalik, Zoltan" sort="Kutalik, Zoltan" uniqKey="Kutalik Z" first="Zoltan" last="Kutalik">Zoltan Kutalik</name><affiliation><nlm:aff id="aff25">Department of Medical Genetics, University of Lausanne, 1005 Lausanne, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="aff26">Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Larson, Martin G" sort="Larson, Martin G" uniqKey="Larson M" first="Martin G." last="Larson">Martin G. Larson</name><affiliation><nlm:aff id="aff9">Framingham Heart Study, Framingham, MA 01702, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff53">Department of Mathematics, Boston University, Boston, MA 02215, USA</nlm:aff></affiliation></author><author><name sortKey="Launer, Lenore J" sort="Launer, Lenore J" uniqKey="Launer L" first="Lenore J." last="Launer">Lenore J. Launer</name><affiliation><nlm:aff id="aff45">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, NIH, Bethesda, MD 20892, USA</nlm:aff></affiliation></author><author><name sortKey="Li, Guo" sort="Li, Guo" uniqKey="Li G" first="Guo" last="Li">Guo Li</name><affiliation><nlm:aff id="aff2">Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA</nlm:aff></affiliation></author><author><name sortKey="Liu, Jianjun" sort="Liu, Jianjun" uniqKey="Liu J" first="Jianjun" last="Liu">Jianjun Liu</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff31">Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore</nlm:aff></affiliation></author><author><name sortKey="Liu, Kiang" sort="Liu, Kiang" uniqKey="Liu K" first="Kiang" last="Liu">Kiang Liu</name><affiliation><nlm:aff id="aff54">Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA</nlm:aff></affiliation></author><author><name sortKey="Morrison, Alanna C" sort="Morrison, Alanna C" uniqKey="Morrison A" first="Alanna C." last="Morrison">Alanna C. Morrison</name><affiliation><nlm:aff id="aff41">Human Genetics Center, University of Texas Health Sciences Center, Houston, TX 77225, USA</nlm:aff></affiliation></author><author><name sortKey="Navis, Gerjan" sort="Navis, Gerjan" uniqKey="Navis G" first="Gerjan" last="Navis">Gerjan Navis</name><affiliation><nlm:aff id="aff55">Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ong, Rick Twee Hee" sort="Ong, Rick Twee Hee" uniqKey="Ong R" first="Rick Twee-Hee" last="Ong">Rick Twee-Hee Ong</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation></author><author><name sortKey="Papanicolau, George J" sort="Papanicolau, George J" uniqKey="Papanicolau G" first="George J." last="Papanicolau">George J. Papanicolau</name><affiliation><nlm:aff id="aff56">Division of Cardiovascular Sciences, National Heart, Lung, & Blood Institute, NIH, Bethesda, MD 20892, USA</nlm:aff></affiliation></author><author><name sortKey="Penninx, Brenda W" sort="Penninx, Brenda W" uniqKey="Penninx B" first="Brenda W." last="Penninx">Brenda W. Penninx</name><affiliation><nlm:aff id="aff57">Department of Psychiatry/EMGO Institute/Neuroscience Campus, VU University Medical Centre, 1081 BT Amsterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff58">Department of Psychiatry, Leiden University Medical Centre, 2333 ZD Leiden, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff59">Department of Psychiatry, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Psaty, Bruce M" sort="Psaty, Bruce M" uniqKey="Psaty B" first="Bruce M." last="Psaty">Bruce M. Psaty</name><affiliation><nlm:aff id="aff2">Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff60">Department of Epidemiology, University of Washington, Seattle, WA 98195, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff61">Department of Health Services, University of Washington, Seattle, WA 98195, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff62">Group Health Research Institute, Group Health Cooperative, Seattle, WA 98101, USA</nlm:aff></affiliation></author><author><name sortKey="Raffel, Leslie J" sort="Raffel, Leslie J" uniqKey="Raffel L" first="Leslie J." last="Raffel">Leslie J. Raffel</name><affiliation><nlm:aff id="aff63">Medical Genetics Institute, Cedars-Sinai Medical Center, Pacific Theatres, Los Angeles, CA 90048, USA</nlm:aff></affiliation></author><author><name sortKey="Raitakari, Olli T" sort="Raitakari, Olli T" uniqKey="Raitakari O" first="Olli T." last="Raitakari">Olli T. Raitakari</name><affiliation><nlm:aff id="aff64">Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20521, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="aff65">Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20521, Finland</nlm:aff></affiliation></author><author><name sortKey="Rice, Kenneth" sort="Rice, Kenneth" uniqKey="Rice K" first="Kenneth" last="Rice">Kenneth Rice</name><affiliation><nlm:aff id="aff66">Department of Biostatistics, University of Washington, Seattle, WA 98195, USA</nlm:aff></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation><nlm:aff id="aff11">Department of Internal Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Rose, Lynda M" sort="Rose, Lynda M" uniqKey="Rose L" first="Lynda M." last="Rose">Lynda M. Rose</name><affiliation><nlm:aff id="aff3">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02215, USA</nlm:aff></affiliation></author><author><name sortKey="Sanna, Serena" sort="Sanna, Serena" uniqKey="Sanna S" first="Serena" last="Sanna">Serena Sanna</name><affiliation><nlm:aff id="aff67">Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato 09042, Italy</nlm:aff></affiliation></author><author><name sortKey="Scott, Robert A" sort="Scott, Robert A" uniqKey="Scott R" first="Robert A." last="Scott">Robert A. Scott</name><affiliation><nlm:aff id="aff35">MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK</nlm:aff></affiliation></author><author><name sortKey="Siscovick, David S" sort="Siscovick, David S" uniqKey="Siscovick D" first="David S." last="Siscovick">David S. Siscovick</name><affiliation><nlm:aff id="aff2">Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff60">Department of Epidemiology, University of Washington, Seattle, WA 98195, USA</nlm:aff></affiliation></author><author><name sortKey="Stolk, Ronald P" sort="Stolk, Ronald P" uniqKey="Stolk R" first="Ronald P." last="Stolk">Ronald P. Stolk</name><affiliation><nlm:aff id="aff38">Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name><affiliation><nlm:aff id="aff11">Department of Internal Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff68">Netherland Genomics Inititiative, Netherlands Center for Healthy Aging, The Hague 2509, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vaidya, Dhananjay" sort="Vaidya, Dhananjay" uniqKey="Vaidya D" first="Dhananjay" last="Vaidya">Dhananjay Vaidya</name><affiliation><nlm:aff id="aff69">Department of Medicine, Johns Hopkins University, Baltimore, MD 21202, USA</nlm:aff></affiliation></author><author><name sortKey="Van Der Klauw, Melanie M" sort="Van Der Klauw, Melanie M" uniqKey="Van Der Klauw M" first="Melanie M." last="Van Der Klauw">Melanie M. Van Der Klauw</name><affiliation><nlm:aff id="aff70">Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vasan, Ramachandran S" sort="Vasan, Ramachandran S" uniqKey="Vasan R" first="Ramachandran S." last="Vasan">Ramachandran S. Vasan</name><affiliation><nlm:aff id="aff9">Framingham Heart Study, Framingham, MA 01702, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff71">Divisions of Epidemiology and Cardiology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA</nlm:aff></affiliation></author><author><name sortKey="Vithana, Eranga Nishanthie" sort="Vithana, Eranga Nishanthie" uniqKey="Vithana E" first="Eranga Nishanthie" last="Vithana">Eranga Nishanthie Vithana</name><affiliation><nlm:aff id="aff21">Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff22">Department of Ophthalmology, National University Health System, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff23">Singapore Eye Research Institute, Singapore 168751, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff72">Neuroscience and Behavioural Disorders (NBD) Program, Duke-NUS Graduate Medical School, Singapore 169857, Singapore</nlm:aff></affiliation></author><author><name sortKey="Volker, Uwe" sort="Volker, Uwe" uniqKey="Volker U" first="Uwe" last="Völker">Uwe Völker</name><affiliation><nlm:aff id="aff73">Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, 17487 Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Volzke, Henry" sort="Volzke, Henry" uniqKey="Volzke H" first="Henry" last="Völzke">Henry Völzke</name><affiliation><nlm:aff id="aff74">Institute for Community Medicine, University of Greifswald, 17487 Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Watkins, Hugh" sort="Watkins, Hugh" uniqKey="Watkins H" first="Hugh" last="Watkins">Hugh Watkins</name><affiliation><nlm:aff id="aff28">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff29">Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK</nlm:aff></affiliation></author><author><name sortKey="Young, Terri L" sort="Young, Terri L" uniqKey="Young T" first="Terri L." last="Young">Terri L. Young</name><affiliation><nlm:aff id="aff75">Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff76">Division of Neuroscience, Duke-National University of Singapore, Singapore 169857, Singapore</nlm:aff></affiliation></author><author><name sortKey="Aung, Tin" sort="Aung, Tin" uniqKey="Aung T" first="Tin" last="Aung">Tin Aung</name><affiliation><nlm:aff id="aff21">Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff22">Department of Ophthalmology, National University Health System, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff23">Singapore Eye Research Institute, Singapore 168751, Singapore</nlm:aff></affiliation></author><author><name sortKey="Bochud, Murielle" sort="Bochud, Murielle" uniqKey="Bochud M" first="Murielle" last="Bochud">Murielle Bochud</name><affiliation><nlm:aff id="aff77">Institute of Social and Preventive Medicine, Lausanne University Hospital, 1010 Lausanne, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Farrall, Martin" sort="Farrall, Martin" uniqKey="Farrall M" first="Martin" last="Farrall">Martin Farrall</name><affiliation><nlm:aff id="aff28">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff29">Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK</nlm:aff></affiliation></author><author><name sortKey="Hartman, Catharina A" sort="Hartman, Catharina A" uniqKey="Hartman C" first="Catharina A." last="Hartman">Catharina A. Hartman</name><affiliation><nlm:aff id="aff78">Interdisciplinary Center for Pathology of Emotions, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Laan, Maris" sort="Laan, Maris" uniqKey="Laan M" first="Maris" last="Laan">Maris Laan</name><affiliation><nlm:aff id="aff40">Human Molecular Genetics Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia</nlm:aff></affiliation></author><author><name sortKey="Lakatta, Edward G" sort="Lakatta, Edward G" uniqKey="Lakatta E" first="Edward G." last="Lakatta">Edward G. Lakatta</name><affiliation><nlm:aff id="aff79">Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Bethesda, MD 21224, USA</nlm:aff></affiliation></author><author><name sortKey="Lehtim Ki, Terho" sort="Lehtim Ki, Terho" uniqKey="Lehtim Ki T" first="Terho" last="Lehtim Ki">Terho Lehtim Ki</name><affiliation><nlm:aff id="aff36">Department of Clinical Chemistry, Fimlab Laboratories, Tampere 30101, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="aff37">Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33101, Finland</nlm:aff></affiliation></author><author><name sortKey="Loos, Ruth J F" sort="Loos, Ruth J F" uniqKey="Loos R" first="Ruth J. F." last="Loos">Ruth J. F. Loos</name><affiliation><nlm:aff id="aff35">MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff80">The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff81">The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff82">The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</nlm:aff></affiliation></author><author><name sortKey="Lucas, Gavin" sort="Lucas, Gavin" uniqKey="Lucas G" first="Gavin" last="Lucas">Gavin Lucas</name><affiliation><nlm:aff id="aff34">Cardiovascular Epidemiology and Genetics, IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Meneton, Pierre" sort="Meneton, Pierre" uniqKey="Meneton P" first="Pierre" last="Meneton">Pierre Meneton</name><affiliation><nlm:aff id="aff83">U872 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Paris 75006, France</nlm:aff></affiliation></author><author><name sortKey="Palmer, Lyle J" sort="Palmer, Lyle J" uniqKey="Palmer L" first="Lyle J." last="Palmer">Lyle J. Palmer</name><affiliation><nlm:aff id="aff17">Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="aff18">Samuel Lunenfeld Research Institute, Toronto, ON M5T 3L9, Canada</nlm:aff></affiliation></author><author><name sortKey="Rettig, Rainer" sort="Rettig, Rainer" uniqKey="Rettig R" first="Rainer" last="Rettig">Rainer Rettig</name><affiliation><nlm:aff id="aff84">Institute of Physiology, University of Greifswald, 17495 Karlsburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Snieder, Harold" sort="Snieder, Harold" uniqKey="Snieder H" first="Harold" last="Snieder">Harold Snieder</name><affiliation><nlm:aff id="aff38">Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Tai, E Shyong" sort="Tai, E Shyong" uniqKey="Tai E" first="E. Shyong" last="Tai">E. Shyong Tai</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff85">Department of Medicine, National University Health System and Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff86">Duke-National University of Singapore Graduate Medical School, Singapore 169857, Singapore</nlm:aff></affiliation></author><author><name sortKey="Teo, Yik Ying" sort="Teo, Yik Ying" uniqKey="Teo Y" first="Yik-Ying" last="Teo">Yik-Ying Teo</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff87">Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff88">Department of Statistics and Applied Probability, National University of Singapore, Singapore 117543, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff89">Genome Institute of Singapore, A<sup>∗</sup>STAR, Singapore 138672, Singapore</nlm:aff></affiliation></author><author><name sortKey="Van Der Harst, Pim" sort="Van Der Harst, Pim" uniqKey="Van Der Harst P" first="Pim" last="Van Der Harst">Pim Van Der Harst</name><affiliation><nlm:aff id="aff27">Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff90">Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff91">Durrer Center for Cardiogenetic Research, 3501 DG Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wareham, Nicholas J" sort="Wareham, Nicholas J" uniqKey="Wareham N" first="Nicholas J." last="Wareham">Nicholas J. Wareham</name><affiliation><nlm:aff id="aff35">MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK</nlm:aff></affiliation></author><author><name sortKey="Wijmenga, Cisca" sort="Wijmenga, Cisca" uniqKey="Wijmenga C" first="Cisca" last="Wijmenga">Cisca Wijmenga</name><affiliation><nlm:aff id="aff90">Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wong, Tien Yin" sort="Wong, Tien Yin" uniqKey="Wong T" first="Tien Yin" last="Wong">Tien Yin Wong</name><affiliation><nlm:aff id="aff21">Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff22">Department of Ophthalmology, National University Health System, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff23">Singapore Eye Research Institute, Singapore 168751, Singapore</nlm:aff></affiliation></author><author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name><affiliation><nlm:aff id="aff7">Research Center for Human Genetics, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff41">Human Genetics Center, University of Texas Health Sciences Center, Houston, TX 77225, USA</nlm:aff></affiliation></author><author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name><affiliation><nlm:aff id="aff12">Icelandic Heart Association, 201 Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="aff13">Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Levy, Daniel" sort="Levy, Daniel" uniqKey="Levy D" first="Daniel" last="Levy">Daniel Levy</name><affiliation><nlm:aff id="aff9">Framingham Heart Study, Framingham, MA 01702, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff10">Center for Population Studies, National Heart, Lung, and Blood Institute, Framingham, MA 01702, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff92">Boston University School of Medicine, Boston, MA 02118, USA</nlm:aff></affiliation></author><author><name sortKey="Palmas, Walter" sort="Palmas, Walter" uniqKey="Palmas W" first="Walter" last="Palmas">Walter Palmas</name><affiliation><nlm:aff id="aff93">Department of Medicine, Columbia University, New York, NY 10032, USA</nlm:aff></affiliation></author><author><name sortKey="Ridker, Paul M" sort="Ridker, Paul M" uniqKey="Ridker P" first="Paul M." last="Ridker">Paul M. Ridker</name><affiliation><nlm:aff id="aff3">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02215, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Harvard Medical School, Boston, MA 02115, USA</nlm:aff></affiliation></author><author><name sortKey="Rotter, Jerome I" sort="Rotter, Jerome I" uniqKey="Rotter J" first="Jerome I." last="Rotter">Jerome I. Rotter</name><affiliation><nlm:aff id="aff8">Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA</nlm:aff></affiliation></author><author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M." last="Van Duijn">Cornelia M. Van Duijn</name><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff68">Netherland Genomics Inititiative, Netherlands Center for Healthy Aging, The Hague 2509, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff94">Netherland Genomics Initiative, Centre for Medical Systems Biology, 2300 RC Leiden, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Witteman, Jacqueline C M" sort="Witteman, Jacqueline C M" uniqKey="Witteman J" first="Jacqueline C. M." last="Witteman">Jacqueline C. M. Witteman</name><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Chakravarti, Aravinda" sort="Chakravarti, Aravinda" uniqKey="Chakravarti A" first="Aravinda" last="Chakravarti">Aravinda Chakravarti</name><affiliation><nlm:aff id="aff5">Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA</nlm:aff></affiliation></author><author><name sortKey="Rao, Dabeeru C" sort="Rao, Dabeeru C" uniqKey="Rao D" first="Dabeeru C." last="Rao">Dabeeru C. Rao</name><affiliation><nlm:aff id="aff1">Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff95">Departments of Psychiatry, Genetics, and Mathematics, Washington University School of Medicine, St. Louis, MO 63110, USA</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24954895</idno><idno type="pmc">4085636</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4085636</idno><idno type="RBID">PMC:4085636</idno><idno type="doi">10.1016/j.ajhg.2014.05.010</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001687</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001687</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Gene-Age Interactions in Blood Pressure Regulation: A Large-Scale Investigation with the CHARGE, Global BPgen, and ICBP Consortia</title><author><name sortKey="Simino, Jeannette" sort="Simino, Jeannette" uniqKey="Simino J" first="Jeannette" last="Simino">Jeannette Simino</name><affiliation><nlm:aff id="aff1">Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA</nlm:aff></affiliation></author><author><name sortKey="Shi, Gang" sort="Shi, Gang" uniqKey="Shi G" first="Gang" last="Shi">Gang Shi</name><affiliation><nlm:aff id="aff1">Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA</nlm:aff></affiliation></author><author><name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua C." last="Bis">Joshua C. Bis</name><affiliation><nlm:aff id="aff2">Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA</nlm:aff></affiliation></author><author><name sortKey="Chasman, Daniel I" sort="Chasman, Daniel I" uniqKey="Chasman D" first="Daniel I." last="Chasman">Daniel I. Chasman</name><affiliation><nlm:aff id="aff3">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02215, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Harvard Medical School, Boston, MA 02115, USA</nlm:aff></affiliation></author><author><name sortKey="Ehret, Georg B" sort="Ehret, Georg B" uniqKey="Ehret G" first="Georg B." last="Ehret">Georg B. Ehret</name><affiliation><nlm:aff id="aff5">Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff6">Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospitals, Geneva 1211, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Gu, Xiangjun" sort="Gu, Xiangjun" uniqKey="Gu X" first="Xiangjun" last="Gu">Xiangjun Gu</name><affiliation><nlm:aff id="aff7">Research Center for Human Genetics, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA</nlm:aff></affiliation></author><author><name sortKey="Guo, Xiuqing" sort="Guo, Xiuqing" uniqKey="Guo X" first="Xiuqing" last="Guo">Xiuqing Guo</name><affiliation><nlm:aff id="aff8">Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA</nlm:aff></affiliation></author><author><name sortKey="Hwang, Shih Jen" sort="Hwang, Shih Jen" uniqKey="Hwang S" first="Shih-Jen" last="Hwang">Shih-Jen Hwang</name><affiliation><nlm:aff id="aff9">Framingham Heart Study, Framingham, MA 01702, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff10">Center for Population Studies, National Heart, Lung, and Blood Institute, Framingham, MA 01702, USA</nlm:aff></affiliation></author><author><name sortKey="Sijbrands, Eric" sort="Sijbrands, Eric" uniqKey="Sijbrands E" first="Eric" last="Sijbrands">Eric Sijbrands</name><affiliation><nlm:aff id="aff11">Department of Internal Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Smith, Albert V" sort="Smith, Albert V" uniqKey="Smith A" first="Albert V." last="Smith">Albert V. Smith</name><affiliation><nlm:aff id="aff12">Icelandic Heart Association, 201 Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="aff13">Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Verwoert, Germaine C" sort="Verwoert, Germaine C" uniqKey="Verwoert G" first="Germaine C." last="Verwoert">Germaine C. Verwoert</name><affiliation><nlm:aff id="aff11">Department of Internal Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Bragg Gresham, Jennifer L" sort="Bragg Gresham, Jennifer L" uniqKey="Bragg Gresham J" first="Jennifer L." last="Bragg-Gresham">Jennifer L. Bragg-Gresham</name><affiliation><nlm:aff id="aff15">Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA</nlm:aff></affiliation></author><author><name sortKey="Cadby, Gemma" sort="Cadby, Gemma" uniqKey="Cadby G" first="Gemma" last="Cadby">Gemma Cadby</name><affiliation><nlm:aff id="aff16">Centre for Genetic Origins of Health and Disease, University of Western Australia, Nedlands, WA 6009, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff17">Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="aff18">Samuel Lunenfeld Research Institute, Toronto, ON M5T 3L9, Canada</nlm:aff></affiliation></author><author><name sortKey="Chen, Peng" sort="Chen, Peng" uniqKey="Chen P" first="Peng" last="Chen">Peng Chen</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation></author><author><name sortKey="Cheng, Ching Yu" sort="Cheng, Ching Yu" uniqKey="Cheng C" first="Ching-Yu" last="Cheng">Ching-Yu Cheng</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff21">Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff22">Department of Ophthalmology, National University Health System, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff23">Singapore Eye Research Institute, Singapore 168751, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff24">Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore 169857, Singapore</nlm:aff></affiliation></author><author><name sortKey="Corre, Tanguy" sort="Corre, Tanguy" uniqKey="Corre T" first="Tanguy" last="Corre">Tanguy Corre</name><affiliation><nlm:aff id="aff25">Department of Medical Genetics, University of Lausanne, 1005 Lausanne, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="aff26">Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland</nlm:aff></affiliation></author><author><name sortKey="De Boer, Rudolf A" sort="De Boer, Rudolf A" uniqKey="De Boer R" first="Rudolf A." last="De Boer">Rudolf A. De Boer</name><affiliation><nlm:aff id="aff27">Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Goel, Anuj" sort="Goel, Anuj" uniqKey="Goel A" first="Anuj" last="Goel">Anuj Goel</name><affiliation><nlm:aff id="aff28">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff29">Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK</nlm:aff></affiliation></author><author><name sortKey="Johnson, Toby" sort="Johnson, Toby" uniqKey="Johnson T" first="Toby" last="Johnson">Toby Johnson</name><affiliation><nlm:aff id="aff30">Clinical Pharmacology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK</nlm:aff></affiliation></author><author><name sortKey="Khor, Chiea Chuen" sort="Khor, Chiea Chuen" uniqKey="Khor C" first="Chiea-Chuen" last="Khor">Chiea-Chuen Khor</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff21">Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff22">Department of Ophthalmology, National University Health System, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff31">Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff32">Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff33">Department of Paediatrics, National University Health System, Singapore 119074, Singapore</nlm:aff></affiliation></author><author><name sortKey="Lluis Ganella, Carla" sort="Lluis Ganella, Carla" uniqKey="Lluis Ganella C" first="Carla" last="Lluís-Ganella">Carla Lluís-Ganella</name><affiliation><nlm:aff id="aff34">Cardiovascular Epidemiology and Genetics, IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Luan, Jian N" sort="Luan, Jian N" uniqKey="Luan J" first="Jian N" last="Luan">Jian N Luan</name><affiliation><nlm:aff id="aff35">MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK</nlm:aff></affiliation></author><author><name sortKey="Lyytik Inen, Leo Pekka" sort="Lyytik Inen, Leo Pekka" uniqKey="Lyytik Inen L" first="Leo-Pekka" last="Lyytik Inen">Leo-Pekka Lyytik Inen</name><affiliation><nlm:aff id="aff36">Department of Clinical Chemistry, Fimlab Laboratories, Tampere 30101, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="aff37">Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33101, Finland</nlm:aff></affiliation></author><author><name sortKey="Nolte, Ilja M" sort="Nolte, Ilja M" uniqKey="Nolte I" first="Ilja M." last="Nolte">Ilja M. Nolte</name><affiliation><nlm:aff id="aff38">Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Sim, Xueling" sort="Sim, Xueling" uniqKey="Sim X" first="Xueling" last="Sim">Xueling Sim</name><affiliation><nlm:aff id="aff15">Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff39">Centre for Molecular Epidemiology, National University of Singapore, Singapore 119260, Singapore</nlm:aff></affiliation></author><author><name sortKey="S Ber, Siim" sort="S Ber, Siim" uniqKey="S Ber S" first="Siim" last="S Ber">Siim S Ber</name><affiliation><nlm:aff id="aff40">Human Molecular Genetics Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia</nlm:aff></affiliation></author><author><name sortKey="Van Der Most, Peter J" sort="Van Der Most, Peter J" uniqKey="Van Der Most P" first="Peter J." last="Van Der Most">Peter J. Van Der Most</name><affiliation><nlm:aff id="aff38">Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Verweij, Niek" sort="Verweij, Niek" uniqKey="Verweij N" first="Niek" last="Verweij">Niek Verweij</name><affiliation><nlm:aff id="aff27">Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zhao, Jing Hua" sort="Zhao, Jing Hua" uniqKey="Zhao J" first="Jing Hua" last="Zhao">Jing Hua Zhao</name><affiliation><nlm:aff id="aff35">MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK</nlm:aff></affiliation></author><author><name sortKey="Amin, Najaf" sort="Amin, Najaf" uniqKey="Amin N" first="Najaf" last="Amin">Najaf Amin</name><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Boerwinkle, Eric" sort="Boerwinkle, Eric" uniqKey="Boerwinkle E" first="Eric" last="Boerwinkle">Eric Boerwinkle</name><affiliation><nlm:aff id="aff41">Human Genetics Center, University of Texas Health Sciences Center, Houston, TX 77225, USA</nlm:aff></affiliation></author><author><name sortKey="Bouchard, Claude" sort="Bouchard, Claude" uniqKey="Bouchard C" first="Claude" last="Bouchard">Claude Bouchard</name><affiliation><nlm:aff id="aff42">Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA</nlm:aff></affiliation></author><author><name sortKey="Dehghan, Abbas" sort="Dehghan, Abbas" uniqKey="Dehghan A" first="Abbas" last="Dehghan">Abbas Dehghan</name><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Eiriksdottir, Gudny" sort="Eiriksdottir, Gudny" uniqKey="Eiriksdottir G" first="Gudny" last="Eiriksdottir">Gudny Eiriksdottir</name><affiliation><nlm:aff id="aff12">Icelandic Heart Association, 201 Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Elosua, Roberto" sort="Elosua, Roberto" uniqKey="Elosua R" first="Roberto" last="Elosua">Roberto Elosua</name><affiliation><nlm:aff id="aff34">Cardiovascular Epidemiology and Genetics, IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain</nlm:aff></affiliation><affiliation><nlm:aff id="aff43">Epidemiology and Public Health Network (CIBERESP), 08036 Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Franco, Oscar H" sort="Franco, Oscar H" uniqKey="Franco O" first="Oscar H." last="Franco">Oscar H. Franco</name><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Gieger, Christian" sort="Gieger, Christian" uniqKey="Gieger C" first="Christian" last="Gieger">Christian Gieger</name><affiliation><nlm:aff id="aff44">Institute of Genetic Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany</nlm:aff></affiliation></author><author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B." last="Harris">Tamara B. Harris</name><affiliation><nlm:aff id="aff45">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, NIH, Bethesda, MD 20892, USA</nlm:aff></affiliation></author><author><name sortKey="Hercberg, Serge" sort="Hercberg, Serge" uniqKey="Hercberg S" first="Serge" last="Hercberg">Serge Hercberg</name><affiliation><nlm:aff id="aff46">U557 Institut National de la Santé et de la Recherche Médicale, U1125 Institut National de la Recherche Agronomique, Université Paris 13, 93000 Bobigny, France</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="James, Alan L" sort="James, Alan L" uniqKey="James A" first="Alan L." last="James">Alan L. James</name><affiliation><nlm:aff id="aff47">Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="aff48">School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA 6009, Australia</nlm:aff></affiliation></author><author><name sortKey="Johnson, Andrew D" sort="Johnson, Andrew D" uniqKey="Johnson A" first="Andrew D." last="Johnson">Andrew D. Johnson</name><affiliation><nlm:aff id="aff9">Framingham Heart Study, Framingham, MA 01702, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff49">Cardiovascular Epidemiology and Human Genomics Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA</nlm:aff></affiliation></author><author><name sortKey="K Honen, Mika" sort="K Honen, Mika" uniqKey="K Honen M" first="Mika" last="K Hönen">Mika K Hönen</name><affiliation><nlm:aff id="aff50">Department of Clinical Physiology, Tampere University Hospital, Tampere 33521, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="aff51">Department of Clinical Physiology, University of Tampere School of Medicine, Tampere 33521, Finland</nlm:aff></affiliation></author><author><name sortKey="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name><affiliation><nlm:aff id="aff52">Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge CB2 2SR, UK</nlm:aff></affiliation></author><author><name sortKey="Kutalik, Zoltan" sort="Kutalik, Zoltan" uniqKey="Kutalik Z" first="Zoltan" last="Kutalik">Zoltan Kutalik</name><affiliation><nlm:aff id="aff25">Department of Medical Genetics, University of Lausanne, 1005 Lausanne, Switzerland</nlm:aff></affiliation><affiliation><nlm:aff id="aff26">Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Larson, Martin G" sort="Larson, Martin G" uniqKey="Larson M" first="Martin G." last="Larson">Martin G. Larson</name><affiliation><nlm:aff id="aff9">Framingham Heart Study, Framingham, MA 01702, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff53">Department of Mathematics, Boston University, Boston, MA 02215, USA</nlm:aff></affiliation></author><author><name sortKey="Launer, Lenore J" sort="Launer, Lenore J" uniqKey="Launer L" first="Lenore J." last="Launer">Lenore J. Launer</name><affiliation><nlm:aff id="aff45">Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, NIH, Bethesda, MD 20892, USA</nlm:aff></affiliation></author><author><name sortKey="Li, Guo" sort="Li, Guo" uniqKey="Li G" first="Guo" last="Li">Guo Li</name><affiliation><nlm:aff id="aff2">Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA</nlm:aff></affiliation></author><author><name sortKey="Liu, Jianjun" sort="Liu, Jianjun" uniqKey="Liu J" first="Jianjun" last="Liu">Jianjun Liu</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff31">Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore</nlm:aff></affiliation></author><author><name sortKey="Liu, Kiang" sort="Liu, Kiang" uniqKey="Liu K" first="Kiang" last="Liu">Kiang Liu</name><affiliation><nlm:aff id="aff54">Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA</nlm:aff></affiliation></author><author><name sortKey="Morrison, Alanna C" sort="Morrison, Alanna C" uniqKey="Morrison A" first="Alanna C." last="Morrison">Alanna C. Morrison</name><affiliation><nlm:aff id="aff41">Human Genetics Center, University of Texas Health Sciences Center, Houston, TX 77225, USA</nlm:aff></affiliation></author><author><name sortKey="Navis, Gerjan" sort="Navis, Gerjan" uniqKey="Navis G" first="Gerjan" last="Navis">Gerjan Navis</name><affiliation><nlm:aff id="aff55">Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ong, Rick Twee Hee" sort="Ong, Rick Twee Hee" uniqKey="Ong R" first="Rick Twee-Hee" last="Ong">Rick Twee-Hee Ong</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation></author><author><name sortKey="Papanicolau, George J" sort="Papanicolau, George J" uniqKey="Papanicolau G" first="George J." last="Papanicolau">George J. Papanicolau</name><affiliation><nlm:aff id="aff56">Division of Cardiovascular Sciences, National Heart, Lung, & Blood Institute, NIH, Bethesda, MD 20892, USA</nlm:aff></affiliation></author><author><name sortKey="Penninx, Brenda W" sort="Penninx, Brenda W" uniqKey="Penninx B" first="Brenda W." last="Penninx">Brenda W. Penninx</name><affiliation><nlm:aff id="aff57">Department of Psychiatry/EMGO Institute/Neuroscience Campus, VU University Medical Centre, 1081 BT Amsterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff58">Department of Psychiatry, Leiden University Medical Centre, 2333 ZD Leiden, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff59">Department of Psychiatry, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Psaty, Bruce M" sort="Psaty, Bruce M" uniqKey="Psaty B" first="Bruce M." last="Psaty">Bruce M. Psaty</name><affiliation><nlm:aff id="aff2">Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff60">Department of Epidemiology, University of Washington, Seattle, WA 98195, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff61">Department of Health Services, University of Washington, Seattle, WA 98195, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff62">Group Health Research Institute, Group Health Cooperative, Seattle, WA 98101, USA</nlm:aff></affiliation></author><author><name sortKey="Raffel, Leslie J" sort="Raffel, Leslie J" uniqKey="Raffel L" first="Leslie J." last="Raffel">Leslie J. Raffel</name><affiliation><nlm:aff id="aff63">Medical Genetics Institute, Cedars-Sinai Medical Center, Pacific Theatres, Los Angeles, CA 90048, USA</nlm:aff></affiliation></author><author><name sortKey="Raitakari, Olli T" sort="Raitakari, Olli T" uniqKey="Raitakari O" first="Olli T." last="Raitakari">Olli T. Raitakari</name><affiliation><nlm:aff id="aff64">Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20521, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="aff65">Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20521, Finland</nlm:aff></affiliation></author><author><name sortKey="Rice, Kenneth" sort="Rice, Kenneth" uniqKey="Rice K" first="Kenneth" last="Rice">Kenneth Rice</name><affiliation><nlm:aff id="aff66">Department of Biostatistics, University of Washington, Seattle, WA 98195, USA</nlm:aff></affiliation></author><author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name><affiliation><nlm:aff id="aff11">Department of Internal Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Rose, Lynda M" sort="Rose, Lynda M" uniqKey="Rose L" first="Lynda M." last="Rose">Lynda M. Rose</name><affiliation><nlm:aff id="aff3">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02215, USA</nlm:aff></affiliation></author><author><name sortKey="Sanna, Serena" sort="Sanna, Serena" uniqKey="Sanna S" first="Serena" last="Sanna">Serena Sanna</name><affiliation><nlm:aff id="aff67">Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato 09042, Italy</nlm:aff></affiliation></author><author><name sortKey="Scott, Robert A" sort="Scott, Robert A" uniqKey="Scott R" first="Robert A." last="Scott">Robert A. Scott</name><affiliation><nlm:aff id="aff35">MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK</nlm:aff></affiliation></author><author><name sortKey="Siscovick, David S" sort="Siscovick, David S" uniqKey="Siscovick D" first="David S." last="Siscovick">David S. Siscovick</name><affiliation><nlm:aff id="aff2">Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff60">Department of Epidemiology, University of Washington, Seattle, WA 98195, USA</nlm:aff></affiliation></author><author><name sortKey="Stolk, Ronald P" sort="Stolk, Ronald P" uniqKey="Stolk R" first="Ronald P." last="Stolk">Ronald P. Stolk</name><affiliation><nlm:aff id="aff38">Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name><affiliation><nlm:aff id="aff11">Department of Internal Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff68">Netherland Genomics Inititiative, Netherlands Center for Healthy Aging, The Hague 2509, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vaidya, Dhananjay" sort="Vaidya, Dhananjay" uniqKey="Vaidya D" first="Dhananjay" last="Vaidya">Dhananjay Vaidya</name><affiliation><nlm:aff id="aff69">Department of Medicine, Johns Hopkins University, Baltimore, MD 21202, USA</nlm:aff></affiliation></author><author><name sortKey="Van Der Klauw, Melanie M" sort="Van Der Klauw, Melanie M" uniqKey="Van Der Klauw M" first="Melanie M." last="Van Der Klauw">Melanie M. Van Der Klauw</name><affiliation><nlm:aff id="aff70">Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Vasan, Ramachandran S" sort="Vasan, Ramachandran S" uniqKey="Vasan R" first="Ramachandran S." last="Vasan">Ramachandran S. Vasan</name><affiliation><nlm:aff id="aff9">Framingham Heart Study, Framingham, MA 01702, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff71">Divisions of Epidemiology and Cardiology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA</nlm:aff></affiliation></author><author><name sortKey="Vithana, Eranga Nishanthie" sort="Vithana, Eranga Nishanthie" uniqKey="Vithana E" first="Eranga Nishanthie" last="Vithana">Eranga Nishanthie Vithana</name><affiliation><nlm:aff id="aff21">Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff22">Department of Ophthalmology, National University Health System, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff23">Singapore Eye Research Institute, Singapore 168751, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff72">Neuroscience and Behavioural Disorders (NBD) Program, Duke-NUS Graduate Medical School, Singapore 169857, Singapore</nlm:aff></affiliation></author><author><name sortKey="Volker, Uwe" sort="Volker, Uwe" uniqKey="Volker U" first="Uwe" last="Völker">Uwe Völker</name><affiliation><nlm:aff id="aff73">Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, 17487 Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Volzke, Henry" sort="Volzke, Henry" uniqKey="Volzke H" first="Henry" last="Völzke">Henry Völzke</name><affiliation><nlm:aff id="aff74">Institute for Community Medicine, University of Greifswald, 17487 Greifswald, Germany</nlm:aff></affiliation></author><author><name sortKey="Watkins, Hugh" sort="Watkins, Hugh" uniqKey="Watkins H" first="Hugh" last="Watkins">Hugh Watkins</name><affiliation><nlm:aff id="aff28">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff29">Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK</nlm:aff></affiliation></author><author><name sortKey="Young, Terri L" sort="Young, Terri L" uniqKey="Young T" first="Terri L." last="Young">Terri L. Young</name><affiliation><nlm:aff id="aff75">Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff76">Division of Neuroscience, Duke-National University of Singapore, Singapore 169857, Singapore</nlm:aff></affiliation></author><author><name sortKey="Aung, Tin" sort="Aung, Tin" uniqKey="Aung T" first="Tin" last="Aung">Tin Aung</name><affiliation><nlm:aff id="aff21">Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff22">Department of Ophthalmology, National University Health System, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff23">Singapore Eye Research Institute, Singapore 168751, Singapore</nlm:aff></affiliation></author><author><name sortKey="Bochud, Murielle" sort="Bochud, Murielle" uniqKey="Bochud M" first="Murielle" last="Bochud">Murielle Bochud</name><affiliation><nlm:aff id="aff77">Institute of Social and Preventive Medicine, Lausanne University Hospital, 1010 Lausanne, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Farrall, Martin" sort="Farrall, Martin" uniqKey="Farrall M" first="Martin" last="Farrall">Martin Farrall</name><affiliation><nlm:aff id="aff28">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff29">Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK</nlm:aff></affiliation></author><author><name sortKey="Hartman, Catharina A" sort="Hartman, Catharina A" uniqKey="Hartman C" first="Catharina A." last="Hartman">Catharina A. Hartman</name><affiliation><nlm:aff id="aff78">Interdisciplinary Center for Pathology of Emotions, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Laan, Maris" sort="Laan, Maris" uniqKey="Laan M" first="Maris" last="Laan">Maris Laan</name><affiliation><nlm:aff id="aff40">Human Molecular Genetics Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia</nlm:aff></affiliation></author><author><name sortKey="Lakatta, Edward G" sort="Lakatta, Edward G" uniqKey="Lakatta E" first="Edward G." last="Lakatta">Edward G. Lakatta</name><affiliation><nlm:aff id="aff79">Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Bethesda, MD 21224, USA</nlm:aff></affiliation></author><author><name sortKey="Lehtim Ki, Terho" sort="Lehtim Ki, Terho" uniqKey="Lehtim Ki T" first="Terho" last="Lehtim Ki">Terho Lehtim Ki</name><affiliation><nlm:aff id="aff36">Department of Clinical Chemistry, Fimlab Laboratories, Tampere 30101, Finland</nlm:aff></affiliation><affiliation><nlm:aff id="aff37">Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33101, Finland</nlm:aff></affiliation></author><author><name sortKey="Loos, Ruth J F" sort="Loos, Ruth J F" uniqKey="Loos R" first="Ruth J. F." last="Loos">Ruth J. F. Loos</name><affiliation><nlm:aff id="aff35">MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff80">The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff81">The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff82">The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</nlm:aff></affiliation></author><author><name sortKey="Lucas, Gavin" sort="Lucas, Gavin" uniqKey="Lucas G" first="Gavin" last="Lucas">Gavin Lucas</name><affiliation><nlm:aff id="aff34">Cardiovascular Epidemiology and Genetics, IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain</nlm:aff></affiliation></author><author><name sortKey="Meneton, Pierre" sort="Meneton, Pierre" uniqKey="Meneton P" first="Pierre" last="Meneton">Pierre Meneton</name><affiliation><nlm:aff id="aff83">U872 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Paris 75006, France</nlm:aff></affiliation></author><author><name sortKey="Palmer, Lyle J" sort="Palmer, Lyle J" uniqKey="Palmer L" first="Lyle J." last="Palmer">Lyle J. Palmer</name><affiliation><nlm:aff id="aff17">Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada</nlm:aff></affiliation><affiliation><nlm:aff id="aff18">Samuel Lunenfeld Research Institute, Toronto, ON M5T 3L9, Canada</nlm:aff></affiliation></author><author><name sortKey="Rettig, Rainer" sort="Rettig, Rainer" uniqKey="Rettig R" first="Rainer" last="Rettig">Rainer Rettig</name><affiliation><nlm:aff id="aff84">Institute of Physiology, University of Greifswald, 17495 Karlsburg, Germany</nlm:aff></affiliation></author><author><name sortKey="Snieder, Harold" sort="Snieder, Harold" uniqKey="Snieder H" first="Harold" last="Snieder">Harold Snieder</name><affiliation><nlm:aff id="aff38">Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Tai, E Shyong" sort="Tai, E Shyong" uniqKey="Tai E" first="E. Shyong" last="Tai">E. Shyong Tai</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff85">Department of Medicine, National University Health System and Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff86">Duke-National University of Singapore Graduate Medical School, Singapore 169857, Singapore</nlm:aff></affiliation></author><author><name sortKey="Teo, Yik Ying" sort="Teo, Yik Ying" uniqKey="Teo Y" first="Yik-Ying" last="Teo">Yik-Ying Teo</name><affiliation><nlm:aff id="aff19">Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff20">Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff87">Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff88">Department of Statistics and Applied Probability, National University of Singapore, Singapore 117543, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff89">Genome Institute of Singapore, A<sup>∗</sup>STAR, Singapore 138672, Singapore</nlm:aff></affiliation></author><author><name sortKey="Van Der Harst, Pim" sort="Van Der Harst, Pim" uniqKey="Van Der Harst P" first="Pim" last="Van Der Harst">Pim Van Der Harst</name><affiliation><nlm:aff id="aff27">Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff90">Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff91">Durrer Center for Cardiogenetic Research, 3501 DG Utrecht, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wareham, Nicholas J" sort="Wareham, Nicholas J" uniqKey="Wareham N" first="Nicholas J." last="Wareham">Nicholas J. Wareham</name><affiliation><nlm:aff id="aff35">MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK</nlm:aff></affiliation></author><author><name sortKey="Wijmenga, Cisca" sort="Wijmenga, Cisca" uniqKey="Wijmenga C" first="Cisca" last="Wijmenga">Cisca Wijmenga</name><affiliation><nlm:aff id="aff90">Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wong, Tien Yin" sort="Wong, Tien Yin" uniqKey="Wong T" first="Tien Yin" last="Wong">Tien Yin Wong</name><affiliation><nlm:aff id="aff21">Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff22">Department of Ophthalmology, National University Health System, Singapore 119228, Singapore</nlm:aff></affiliation><affiliation><nlm:aff id="aff23">Singapore Eye Research Institute, Singapore 168751, Singapore</nlm:aff></affiliation></author><author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name><affiliation><nlm:aff id="aff7">Research Center for Human Genetics, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff41">Human Genetics Center, University of Texas Health Sciences Center, Houston, TX 77225, USA</nlm:aff></affiliation></author><author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name><affiliation><nlm:aff id="aff12">Icelandic Heart Association, 201 Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="aff13">Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Levy, Daniel" sort="Levy, Daniel" uniqKey="Levy D" first="Daniel" last="Levy">Daniel Levy</name><affiliation><nlm:aff id="aff9">Framingham Heart Study, Framingham, MA 01702, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff10">Center for Population Studies, National Heart, Lung, and Blood Institute, Framingham, MA 01702, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff92">Boston University School of Medicine, Boston, MA 02118, USA</nlm:aff></affiliation></author><author><name sortKey="Palmas, Walter" sort="Palmas, Walter" uniqKey="Palmas W" first="Walter" last="Palmas">Walter Palmas</name><affiliation><nlm:aff id="aff93">Department of Medicine, Columbia University, New York, NY 10032, USA</nlm:aff></affiliation></author><author><name sortKey="Ridker, Paul M" sort="Ridker, Paul M" uniqKey="Ridker P" first="Paul M." last="Ridker">Paul M. Ridker</name><affiliation><nlm:aff id="aff3">Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02215, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Harvard Medical School, Boston, MA 02115, USA</nlm:aff></affiliation></author><author><name sortKey="Rotter, Jerome I" sort="Rotter, Jerome I" uniqKey="Rotter J" first="Jerome I." last="Rotter">Jerome I. Rotter</name><affiliation><nlm:aff id="aff8">Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA</nlm:aff></affiliation></author><author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M." last="Van Duijn">Cornelia M. Van Duijn</name><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff68">Netherland Genomics Inititiative, Netherlands Center for Healthy Aging, The Hague 2509, the Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="aff94">Netherland Genomics Initiative, Centre for Medical Systems Biology, 2300 RC Leiden, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Witteman, Jacqueline C M" sort="Witteman, Jacqueline C M" uniqKey="Witteman J" first="Jacqueline C. M." last="Witteman">Jacqueline C. M. Witteman</name><affiliation><nlm:aff id="aff14">Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</nlm:aff></affiliation></author><author><name sortKey="Chakravarti, Aravinda" sort="Chakravarti, Aravinda" uniqKey="Chakravarti A" first="Aravinda" last="Chakravarti">Aravinda Chakravarti</name><affiliation><nlm:aff id="aff5">Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA</nlm:aff></affiliation></author><author><name sortKey="Rao, Dabeeru C" sort="Rao, Dabeeru C" uniqKey="Rao D" first="Dabeeru C." last="Rao">Dabeeru C. Rao</name><affiliation><nlm:aff id="aff1">Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA</nlm:aff></affiliation><affiliation><nlm:aff id="aff95">Departments of Psychiatry, Genetics, and Mathematics, Washington University School of Medicine, St. Louis, MO 63110, USA</nlm:aff></affiliation></author></analytic><series><title level="j">American Journal of Human Genetics</title><idno type="ISSN">0002-9297</idno><idno type="eISSN">1537-6605</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p ≤ 5 × 10<sup>−8</sup>) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the <italic>EHBP1L1</italic> (DBP and MAP), <italic>CASZ1</italic> (SBP and MAP), and <italic>GOSR2</italic> (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The <italic>EHBP1L1</italic> locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 × 10<sup>−4</sup>) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Am J Hum Genet</journal-id><journal-id journal-id-type="iso-abbrev">Am. J. Hum. Genet</journal-id><journal-title-group><journal-title>American Journal of Human Genetics</journal-title></journal-title-group><issn pub-type="ppub">0002-9297</issn><issn pub-type="epub">1537-6605</issn><publisher><publisher-name>Elsevier</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24954895</article-id><article-id pub-id-type="pmc">4085636</article-id><article-id pub-id-type="publisher-id">S0002-9297(14)00230-4</article-id><article-id pub-id-type="doi">10.1016/j.ajhg.2014.05.010</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Gene-Age Interactions in Blood Pressure Regulation: A Large-Scale Investigation with the CHARGE, Global BPgen, and ICBP Consortia</article-title></title-group><contrib-group><contrib 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contrib-type="author"><name><surname>Rosmalen</surname><given-names>Judith G.M.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Slaets</surname><given-names>Joris P.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Snieder</surname><given-names>Harold</given-names></name></contrib><contrib contrib-type="author"><name><surname>Stolk</surname><given-names>Ronald P.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Wolffenbuttel</surname><given-names>Bruce H.R.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Wijmenga</surname><given-names>Cisca</given-names></name></contrib></contrib-group></collab></contrib><contrib contrib-type="author"><name><surname>Lluís-Ganella</surname><given-names>Carla</given-names></name><xref rid="aff34" ref-type="aff">34</xref></contrib><contrib contrib-type="author"><name><surname>Luan</surname><given-names>Jian’an</given-names></name><xref rid="aff35" ref-type="aff">35</xref></contrib><contrib contrib-type="author"><name><surname>Lyytikäinen</surname><given-names>Leo-Pekka</given-names></name><xref rid="aff36" ref-type="aff">36</xref><xref rid="aff37" ref-type="aff">37</xref></contrib><contrib contrib-type="author"><name><surname>Nolte</surname><given-names>Ilja M.</given-names></name><xref rid="aff38" ref-type="aff">38</xref></contrib><contrib contrib-type="author"><name><surname>Sim</surname><given-names>Xueling</given-names></name><xref rid="aff15" ref-type="aff">15</xref><xref rid="aff39" ref-type="aff">39</xref></contrib><contrib contrib-type="author"><name><surname>Sõber</surname><given-names>Siim</given-names></name><xref rid="aff40" ref-type="aff">40</xref></contrib><contrib contrib-type="author"><name><surname>van der Most</surname><given-names>Peter J.</given-names></name><xref rid="aff38" ref-type="aff">38</xref></contrib><contrib contrib-type="author"><name><surname>Verweij</surname><given-names>Niek</given-names></name><xref rid="aff27" ref-type="aff">27</xref></contrib><contrib contrib-type="author"><name><surname>Zhao</surname><given-names>Jing Hua</given-names></name><xref rid="aff35" ref-type="aff">35</xref></contrib><contrib contrib-type="author"><name><surname>Amin</surname><given-names>Najaf</given-names></name><xref rid="aff14" ref-type="aff">14</xref></contrib><contrib contrib-type="author"><name><surname>Boerwinkle</surname><given-names>Eric</given-names></name><xref rid="aff41" ref-type="aff">41</xref></contrib><contrib contrib-type="author"><name><surname>Bouchard</surname><given-names>Claude</given-names></name><xref rid="aff42" ref-type="aff">42</xref></contrib><contrib contrib-type="author"><name><surname>Dehghan</surname><given-names>Abbas</given-names></name><xref rid="aff14" ref-type="aff">14</xref></contrib><contrib 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contrib-type="author"><name><surname>Morrison</surname><given-names>Alanna C.</given-names></name><xref rid="aff41" ref-type="aff">41</xref></contrib><contrib contrib-type="author"><name><surname>Navis</surname><given-names>Gerjan</given-names></name><xref rid="aff55" ref-type="aff">55</xref></contrib><contrib contrib-type="author"><name><surname>Ong</surname><given-names>Rick Twee-Hee</given-names></name><xref rid="aff19" ref-type="aff">19</xref><xref rid="aff20" ref-type="aff">20</xref></contrib><contrib contrib-type="author"><name><surname>Papanicolau</surname><given-names>George J.</given-names></name><xref rid="aff56" ref-type="aff">56</xref></contrib><contrib contrib-type="author"><name><surname>Penninx</surname><given-names>Brenda W.</given-names></name><xref rid="aff57" ref-type="aff">57</xref><xref rid="aff58" ref-type="aff">58</xref><xref rid="aff59" ref-type="aff">59</xref></contrib><contrib contrib-type="author"><name><surname>Psaty</surname><given-names>Bruce 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contrib-type="author"><name><surname>Vaidya</surname><given-names>Dhananjay</given-names></name><xref rid="aff69" ref-type="aff">69</xref></contrib><contrib contrib-type="author"><name><surname>van der Klauw</surname><given-names>Melanie M.</given-names></name><xref rid="aff70" ref-type="aff">70</xref></contrib><contrib contrib-type="author"><name><surname>Vasan</surname><given-names>Ramachandran S.</given-names></name><xref rid="aff9" ref-type="aff">9</xref><xref rid="aff71" ref-type="aff">71</xref></contrib><contrib contrib-type="author"><name><surname>Vithana</surname><given-names>Eranga Nishanthie</given-names></name><xref rid="aff21" ref-type="aff">21</xref><xref rid="aff22" ref-type="aff">22</xref><xref rid="aff23" ref-type="aff">23</xref><xref rid="aff72" ref-type="aff">72</xref></contrib><contrib contrib-type="author"><name><surname>Völker</surname><given-names>Uwe</given-names></name><xref rid="aff73" ref-type="aff">73</xref></contrib><contrib contrib-type="author"><name><surname>Völzke</surname><given-names>Henry</given-names></name><xref rid="aff74" ref-type="aff">74</xref></contrib><contrib contrib-type="author"><name><surname>Watkins</surname><given-names>Hugh</given-names></name><xref rid="aff28" ref-type="aff">28</xref><xref rid="aff29" ref-type="aff">29</xref></contrib><contrib contrib-type="author"><name><surname>Young</surname><given-names>Terri L.</given-names></name><xref rid="aff75" ref-type="aff">75</xref><xref rid="aff76" ref-type="aff">76</xref></contrib><contrib contrib-type="author"><name><surname>Aung</surname><given-names>Tin</given-names></name><xref rid="aff21" ref-type="aff">21</xref><xref rid="aff22" ref-type="aff">22</xref><xref rid="aff23" ref-type="aff">23</xref></contrib><contrib contrib-type="author"><name><surname>Bochud</surname><given-names>Murielle</given-names></name><xref rid="aff77" ref-type="aff">77</xref></contrib><contrib contrib-type="author"><name><surname>Farrall</surname><given-names>Martin</given-names></name><xref rid="aff28" ref-type="aff">28</xref><xref rid="aff29" ref-type="aff">29</xref></contrib><contrib contrib-type="author"><name><surname>Hartman</surname><given-names>Catharina A.</given-names></name><xref rid="aff78" ref-type="aff">78</xref></contrib><contrib contrib-type="author"><name><surname>Laan</surname><given-names>Maris</given-names></name><xref rid="aff40" ref-type="aff">40</xref></contrib><contrib contrib-type="author"><name><surname>Lakatta</surname><given-names>Edward G.</given-names></name><xref rid="aff79" ref-type="aff">79</xref></contrib><contrib contrib-type="author"><name><surname>Lehtimäki</surname><given-names>Terho</given-names></name><xref rid="aff36" ref-type="aff">36</xref><xref rid="aff37" ref-type="aff">37</xref></contrib><contrib contrib-type="author"><name><surname>Loos</surname><given-names>Ruth J.F.</given-names></name><xref rid="aff35" ref-type="aff">35</xref><xref rid="aff80" ref-type="aff">80</xref><xref rid="aff81" ref-type="aff">81</xref><xref rid="aff82" ref-type="aff">82</xref></contrib><contrib contrib-type="author"><name><surname>Lucas</surname><given-names>Gavin</given-names></name><xref rid="aff34" ref-type="aff">34</xref></contrib><contrib contrib-type="author"><name><surname>Meneton</surname><given-names>Pierre</given-names></name><xref rid="aff83" ref-type="aff">83</xref></contrib><contrib contrib-type="author"><name><surname>Palmer</surname><given-names>Lyle J.</given-names></name><xref rid="aff17" ref-type="aff">17</xref><xref rid="aff18" ref-type="aff">18</xref></contrib><contrib contrib-type="author"><name><surname>Rettig</surname><given-names>Rainer</given-names></name><xref rid="aff84" ref-type="aff">84</xref></contrib><contrib contrib-type="author"><name><surname>Snieder</surname><given-names>Harold</given-names></name><xref rid="aff38" ref-type="aff">38</xref></contrib><contrib contrib-type="author"><name><surname>Tai</surname><given-names>E. Shyong</given-names></name><xref rid="aff19" ref-type="aff">19</xref><xref rid="aff20" ref-type="aff">20</xref><xref rid="aff85" ref-type="aff">85</xref><xref rid="aff86" ref-type="aff">86</xref></contrib><contrib contrib-type="author"><name><surname>Teo</surname><given-names>Yik-Ying</given-names></name><xref rid="aff19" ref-type="aff">19</xref><xref rid="aff20" ref-type="aff">20</xref><xref rid="aff87" ref-type="aff">87</xref><xref rid="aff88" ref-type="aff">88</xref><xref rid="aff89" ref-type="aff">89</xref></contrib><contrib contrib-type="author"><name><surname>van der Harst</surname><given-names>Pim</given-names></name><xref rid="aff27" ref-type="aff">27</xref><xref rid="aff90" ref-type="aff">90</xref><xref rid="aff91" ref-type="aff">91</xref></contrib><contrib contrib-type="author"><name><surname>Wareham</surname><given-names>Nicholas J.</given-names></name><xref rid="aff35" ref-type="aff">35</xref></contrib><contrib contrib-type="author"><name><surname>Wijmenga</surname><given-names>Cisca</given-names></name><xref rid="aff90" ref-type="aff">90</xref></contrib><contrib contrib-type="author"><name><surname>Wong</surname><given-names>Tien Yin</given-names></name><xref rid="aff21" ref-type="aff">21</xref><xref rid="aff22" ref-type="aff">22</xref><xref rid="aff23" ref-type="aff">23</xref></contrib><contrib contrib-type="author"><name><surname>Fornage</surname><given-names>Myriam</given-names></name><xref rid="aff7" ref-type="aff">7</xref><xref rid="aff41" ref-type="aff">41</xref><xref rid="fn1" ref-type="fn">96</xref></contrib><contrib contrib-type="author"><name><surname>Gudnason</surname><given-names>Vilmundur</given-names></name><xref rid="aff12" ref-type="aff">12</xref><xref rid="aff13" ref-type="aff">13</xref><xref rid="fn1" ref-type="fn">96</xref></contrib><contrib contrib-type="author"><name><surname>Levy</surname><given-names>Daniel</given-names></name><xref rid="aff9" ref-type="aff">9</xref><xref rid="aff10" ref-type="aff">10</xref><xref rid="aff92" ref-type="aff">92</xref><xref rid="fn1" ref-type="fn">96</xref></contrib><contrib contrib-type="author"><name><surname>Palmas</surname><given-names>Walter</given-names></name><xref rid="aff93" ref-type="aff">93</xref><xref rid="fn1" ref-type="fn">96</xref></contrib><contrib contrib-type="author"><name><surname>Ridker</surname><given-names>Paul M.</given-names></name><xref rid="aff3" ref-type="aff">3</xref><xref rid="aff4" ref-type="aff">4</xref><xref rid="fn1" ref-type="fn">96</xref></contrib><contrib contrib-type="author"><name><surname>Rotter</surname><given-names>Jerome I.</given-names></name><xref rid="aff8" ref-type="aff">8</xref><xref rid="fn1" ref-type="fn">96</xref></contrib><contrib contrib-type="author"><name><surname>van Duijn</surname><given-names>Cornelia M.</given-names></name><xref rid="aff14" ref-type="aff">14</xref><xref rid="aff68" ref-type="aff">68</xref><xref rid="aff94" ref-type="aff">94</xref><xref rid="fn1" ref-type="fn">96</xref></contrib><contrib contrib-type="author"><name><surname>Witteman</surname><given-names>Jacqueline C.M.</given-names></name><xref rid="aff14" ref-type="aff">14</xref><xref rid="fn1" ref-type="fn">96</xref></contrib><contrib contrib-type="author"><name><surname>Chakravarti</surname><given-names>Aravinda</given-names></name><email>aravinda@jhmi.edu</email><xref rid="aff5" ref-type="aff">5</xref><xref rid="fn1" ref-type="fn">96</xref><xref rid="cor2" ref-type="corresp">∗∗</xref></contrib><contrib contrib-type="author"><name><surname>Rao</surname><given-names>Dabeeru C.</given-names></name><xref rid="aff1" ref-type="aff">1</xref><xref rid="aff95" ref-type="aff">95</xref><xref rid="fn1" ref-type="fn">96</xref></contrib></contrib-group><aff id="aff1"><label>1</label>Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA</aff><aff id="aff2"><label>2</label>Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA</aff><aff id="aff3"><label>3</label>Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02215, USA</aff><aff id="aff4"><label>4</label>Harvard Medical School, Boston, MA 02115, USA</aff><aff id="aff5"><label>5</label>Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA</aff><aff id="aff6"><label>6</label>Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospitals, Geneva 1211, Switzerland</aff><aff id="aff7"><label>7</label>Research Center for Human Genetics, Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX 77030, USA</aff><aff id="aff8"><label>8</label>Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA</aff><aff id="aff9"><label>9</label>Framingham Heart Study, Framingham, MA 01702, USA</aff><aff id="aff10"><label>10</label>Center for Population Studies, National Heart, Lung, and Blood Institute, Framingham, MA 01702, USA</aff><aff id="aff11"><label>11</label>Department of Internal Medicine, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</aff><aff id="aff12"><label>12</label>Icelandic Heart Association, 201 Kopavogur, Iceland</aff><aff id="aff13"><label>13</label>Faculty of Medicine, University of Iceland, 101 Reykjavik, Iceland</aff><aff id="aff14"><label>14</label>Department of Epidemiology, Erasmus University Medical Center, 3015 GE Rotterdam, the Netherlands</aff><aff id="aff15"><label>15</label>Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA</aff><aff id="aff16"><label>16</label>Centre for Genetic Origins of Health and Disease, University of Western Australia, Nedlands, WA 6009, Australia</aff><aff id="aff17"><label>17</label>Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada</aff><aff id="aff18"><label>18</label>Samuel Lunenfeld Research Institute, Toronto, ON M5T 3L9, Canada</aff><aff id="aff19"><label>19</label>Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117597, Singapore</aff><aff id="aff20"><label>20</label>Saw Swee Hock School of Public Health, National University Health System, Singapore 117597, Singapore</aff><aff id="aff21"><label>21</label>Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</aff><aff id="aff22"><label>22</label>Department of Ophthalmology, National University Health System, Singapore 119228, Singapore</aff><aff id="aff23"><label>23</label>Singapore Eye Research Institute, Singapore 168751, Singapore</aff><aff id="aff24"><label>24</label>Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore 169857, Singapore</aff><aff id="aff25"><label>25</label>Department of Medical Genetics, University of Lausanne, 1005 Lausanne, Switzerland</aff><aff id="aff26"><label>26</label>Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland</aff><aff id="aff27"><label>27</label>Department of Cardiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</aff><aff id="aff28"><label>28</label>Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK</aff><aff id="aff29"><label>29</label>Division of Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DU, UK</aff><aff id="aff30"><label>30</label>Clinical Pharmacology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK</aff><aff id="aff31"><label>31</label>Division of Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore</aff><aff id="aff32"><label>32</label>Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</aff><aff id="aff33"><label>33</label>Department of Paediatrics, National University Health System, Singapore 119074, Singapore</aff><aff id="aff34"><label>34</label>Cardiovascular Epidemiology and Genetics, IMIM (Hospital del Mar Medical Research Institute), 08003 Barcelona, Spain</aff><aff id="aff35"><label>35</label>MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge CB2 0QQ, UK</aff><aff id="aff36"><label>36</label>Department of Clinical Chemistry, Fimlab Laboratories, Tampere 30101, Finland</aff><aff id="aff37"><label>37</label>Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere 33101, Finland</aff><aff id="aff38"><label>38</label>Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</aff><aff id="aff39"><label>39</label>Centre for Molecular Epidemiology, National University of Singapore, Singapore 119260, Singapore</aff><aff id="aff40"><label>40</label>Human Molecular Genetics Group, Institute of Molecular and Cell Biology, University of Tartu, Tartu 51010, Estonia</aff><aff id="aff41"><label>41</label>Human Genetics Center, University of Texas Health Sciences Center, Houston, TX 77225, USA</aff><aff id="aff42"><label>42</label>Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA</aff><aff id="aff43"><label>43</label>Epidemiology and Public Health Network (CIBERESP), 08036 Barcelona, Spain</aff><aff id="aff44"><label>44</label>Institute of Genetic Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany</aff><aff id="aff45"><label>45</label>Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, NIH, Bethesda, MD 20892, USA</aff><aff id="aff46"><label>46</label>U557 Institut National de la Santé et de la Recherche Médicale, U1125 Institut National de la Recherche Agronomique, Université Paris 13, 93000 Bobigny, France</aff><aff id="aff47"><label>47</label>Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital, Nedlands, WA 6009, Australia</aff><aff id="aff48"><label>48</label>School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA 6009, Australia</aff><aff id="aff49"><label>49</label>Cardiovascular Epidemiology and Human Genomics Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA</aff><aff id="aff50"><label>50</label>Department of Clinical Physiology, Tampere University Hospital, Tampere 33521, Finland</aff><aff id="aff51"><label>51</label>Department of Clinical Physiology, University of Tampere School of Medicine, Tampere 33521, Finland</aff><aff id="aff52"><label>52</label>Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge CB2 2SR, UK</aff><aff id="aff53"><label>53</label>Department of Mathematics, Boston University, Boston, MA 02215, USA</aff><aff id="aff54"><label>54</label>Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA</aff><aff id="aff55"><label>55</label>Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</aff><aff id="aff56"><label>56</label>Division of Cardiovascular Sciences, National Heart, Lung, & Blood Institute, NIH, Bethesda, MD 20892, USA</aff><aff id="aff57"><label>57</label>Department of Psychiatry/EMGO Institute/Neuroscience Campus, VU University Medical Centre, 1081 BT Amsterdam, the Netherlands</aff><aff id="aff58"><label>58</label>Department of Psychiatry, Leiden University Medical Centre, 2333 ZD Leiden, the Netherlands</aff><aff id="aff59"><label>59</label>Department of Psychiatry, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</aff><aff id="aff60"><label>60</label>Department of Epidemiology, University of Washington, Seattle, WA 98195, USA</aff><aff id="aff61"><label>61</label>Department of Health Services, University of Washington, Seattle, WA 98195, USA</aff><aff id="aff62"><label>62</label>Group Health Research Institute, Group Health Cooperative, Seattle, WA 98101, USA</aff><aff id="aff63"><label>63</label>Medical Genetics Institute, Cedars-Sinai Medical Center, Pacific Theatres, Los Angeles, CA 90048, USA</aff><aff id="aff64"><label>64</label>Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20521, Finland</aff><aff id="aff65"><label>65</label>Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20521, Finland</aff><aff id="aff66"><label>66</label>Department of Biostatistics, University of Washington, Seattle, WA 98195, USA</aff><aff id="aff67"><label>67</label>Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato 09042, Italy</aff><aff id="aff68"><label>68</label>Netherland Genomics Inititiative, Netherlands Center for Healthy Aging, The Hague 2509, the Netherlands</aff><aff id="aff69"><label>69</label>Department of Medicine, Johns Hopkins University, Baltimore, MD 21202, USA</aff><aff id="aff70"><label>70</label>Department of Endocrinology, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</aff><aff id="aff71"><label>71</label>Divisions of Epidemiology and Cardiology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA</aff><aff id="aff72"><label>72</label>Neuroscience and Behavioural Disorders (NBD) Program, Duke-NUS Graduate Medical School, Singapore 169857, Singapore</aff><aff id="aff73"><label>73</label>Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, 17487 Greifswald, Germany</aff><aff id="aff74"><label>74</label>Institute for Community Medicine, University of Greifswald, 17487 Greifswald, Germany</aff><aff id="aff75"><label>75</label>Department of Ophthalmology, Duke University Medical Center, Durham, NC 27710, USA</aff><aff id="aff76"><label>76</label>Division of Neuroscience, Duke-National University of Singapore, Singapore 169857, Singapore</aff><aff id="aff77"><label>77</label>Institute of Social and Preventive Medicine, Lausanne University Hospital, 1010 Lausanne, Switzerland</aff><aff id="aff78"><label>78</label>Interdisciplinary Center for Pathology of Emotions, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</aff><aff id="aff79"><label>79</label>Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Bethesda, MD 21224, USA</aff><aff id="aff80"><label>80</label>The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</aff><aff id="aff81"><label>81</label>The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</aff><aff id="aff82"><label>82</label>The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA</aff><aff id="aff83"><label>83</label>U872 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Paris 75006, France</aff><aff id="aff84"><label>84</label>Institute of Physiology, University of Greifswald, 17495 Karlsburg, Germany</aff><aff id="aff85"><label>85</label>Department of Medicine, National University Health System and Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore</aff><aff id="aff86"><label>86</label>Duke-National University of Singapore Graduate Medical School, Singapore 169857, Singapore</aff><aff id="aff87"><label>87</label>Life Sciences Institute, National University of Singapore, Singapore 117456, Singapore</aff><aff id="aff88"><label>88</label>Department of Statistics and Applied Probability, National University of Singapore, Singapore 117543, Singapore</aff><aff id="aff89"><label>89</label>Genome Institute of Singapore, A<sup>∗</sup>STAR, Singapore 138672, Singapore</aff><aff id="aff90"><label>90</label>Department of Genetics, University of Groningen, University Medical Center Groningen, 9700 RB Groningen, the Netherlands</aff><aff id="aff91"><label>91</label>Durrer Center for Cardiogenetic Research, 3501 DG Utrecht, the Netherlands</aff><aff id="aff92"><label>92</label>Boston University School of Medicine, Boston, MA 02118, USA</aff><aff id="aff93"><label>93</label>Department of Medicine, Columbia University, New York, NY 10032, USA</aff><aff id="aff94"><label>94</label>Netherland Genomics Initiative, Centre for Medical Systems Biology, 2300 RC Leiden, the Netherlands</aff><aff id="aff95"><label>95</label>Departments of Psychiatry, Genetics, and Mathematics, Washington University School of Medicine, St. Louis, MO 63110, USA</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author <email>jeannette@wubios.wustl.edu</email></corresp><corresp id="cor2"><label>∗∗</label>Corresponding author <email>aravinda@jhmi.edu</email></corresp><fn id="fn1"><label>96</label><p>These authors contributed equally to this work</p></fn></author-notes><pub-date pub-type="ppub"><day>03</day><month>7</month><year>2014</year></pub-date><volume>95</volume><issue>1</issue><fpage>24</fpage><lpage>38</lpage><history><date date-type="received"><day>22</day><month>2</month><year>2014</year></date><date date-type="accepted"><day>20</day><month>5</month><year>2014</year></date></history><permissions><copyright-statement>© 2014 The American Society of Human Genetics. Published by Elsevier Ltd. All right reserved.</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>The American Society of Human Genetics</copyright-holder></permissions><abstract><p>Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p ≤ 5 × 10<sup>−8</sup>) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the <italic>EHBP1L1</italic> (DBP and MAP), <italic>CASZ1</italic> (SBP and MAP), and <italic>GOSR2</italic> (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The <italic>EHBP1L1</italic> locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 × 10<sup>−4</sup>) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations.</p></abstract></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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