Tianxiao Huan, Tõnu Esko, Marjolein J. Peters, Luke C. Pilling, Katharina Schramm, Claudia Schurmann, Brian H. Chen, Chunyu Liu, Roby Joehanes, Andrew D. Johnson, Chen Yao, Sai-xia Ying, Paul Courchesne, Lili Milani, Nalini Raghavachari, Richard Wang, Poching Liu, Eva Reinmaa, Abbas Dehghan, Albert Hofman, André G. Uitterlinden, Dena G. Hernandez, Stefania Bandinelli, Andrew Singleton, David Melzer, Andres Metspalu, Maren Carstensen, Harald Grallert, Christian Herder, Thomas Meitinger, Annette Peters, Michael Roden, Melanie Waldenberger, Marcus Dörr, Stephan B. Felix, Tanja Zeller, Ramachandran S. Vasan, Christopher J. O'Donnell, Peter J. Munson, Xia Yang, Holger Prokisch, Uwe Völker, Joyce B. J. van Meurs, Luigi Ferrucci, Daniel Levy, Georg B. Ehret, Patricia B. Munroe, Kenneth M. Rice, Murielle Bochud, Daniel I. Chasman, Albert V. Smith, Martin D. Tobin, Germaine C. Verwoert, Shih-Jen Hwang, Vasyl Pihur, Peter Vollenweider, Paul F. O’Reilly, Najaf Amin, Jennifer L. Bragg-Gresham, Alexander Teumer, Nicole L. Glazer, Lenore Launer, Jing Hua Zhao, Yurii Aulchenko, Simon Heath, Siim Sõber, Afshin Parsa, Jian’an Luan, Pankaj Arora, Feng Zhang, Gavin Lucas, Andrew A. Hicks, Anne U. Jackson, John F. Peden, Toshiko Tanaka, Sarah H. Wild, Igor Rudan, Wilmar Igl, Yuri Milaneschi, Alex N. Parker, Cristiano Fava, John C. Chambers, Ervin R. Fox, Meena Kumari, Min Jin Go, Pim van der Harst, Wen Hong Linda Kao, Marketa Sjögren, D.G. Vinay, Myriam Alexander, Yasuharu Tabara, Sue Shaw-Hawkins, Peter H. Whincup, Yongmei Liu, Gang Shi, Johanna Kuusisto, Bamidele Tayo, Mark Seielstad, Xueling Sim, Khanh-Dung Hoang Nguyen, Terho Lehtimäki, Giuseppe Matullo, Ying Wu, Tom R. Gaunt, N. Charlotte Onland-Moret, Matthew N. Cooper, Carl G.P. Platou, Elin Org, Rebecca Hardy, Santosh Dahgam, Jutta Palmen, Veronique Vitart, Peter S. Braund, Tatiana Kuznetsova, Cuno S.P.M. Uiterwaal, Adebowale Adeyemo, Walter Palmas, Harry Campbell, Barbara Ludwig, Maciej Tomaszewski, Ioanna Tzoulaki, Nicholette D. Palmer, Thor Aspelund, Melissa Garcia, Yen-Pei C. Chang, Jeffrey R. O’Connell, Nanette I. Steinle, Diederick E. Grobbee, Dan E. Arking, Sharon L. Kardia, Alanna C. Morrison, Samer Najjar, Wendy L. McArdle, David Hadley, Morris J. Brown, John M. Connell, Aroon D. Hingorani, Ian N.M. Day, Debbie A. Lawlor, Robert W. Lawrence, Robert Clarke, Rory Collins, Jemma C. Hopewell, Halit Ongen, Albert W. Dreisbach, Yali Li, J.H. Young, Joshua C. Bis, Mika Kähönen, Jorma Viikari, Linda S. Adair, Nanette R. Lee, Ming-Huei Chen, Matthias Olden, Cristian Pattaro, Judith A. Hoffman Bolton, Anna Köttgen, Sven Bergmann, Vincent Mooser, Nish Chaturvedi, Timothy M. Frayling, Muhammad Islam, Tazeen H. Jafar, Jeanette Erdmann, Smita R. Kulkarni, Stefan R. Bornstein, Jürgen Grässler, Leif Groop, Benjamin F. Voight, Johannes Kettunen, Philip Howard, Andrew Taylor, Simonetta Guarrera, Fulvio Ricceri, Valur Emilsson, Andrew Plump, Inês Barroso, Kay-Tee Khaw, Alan B. Weder, Steven C. Hunt, Yan V. Sun, Richard N. Bergman, Lori L. Bonnycastle, Laura J. Scott, Heather M. Stringham, Markus Perola, Erkki Vartiainen, Stefan-Martin Brand, Jan A. Staessen, Thomas J. Wang, Paul R. Burton, Maria Soler Artigas, Yanbin Dong, Harold Snieder, Xiaoling Wang, Haidong Zhu, Kurt K. Lohman, Megan E. Rudock, Susan R. Heckbert, Nicholas L. Smith, Kerri L. Wiggins, Ayo Doumatey, Daniel Shriner, Gudrun Veldre, Margus Viigimaa, Sanjay Kinra, Dorairajan Prabhakaran, Vikal Tripathy, Carl D. Langefeld, Annika Rosengren, Dag S. Thelle, AnnaCorsi Maria, Terrence Forrester, Gina Hilton, Colin A. McKenzie, Tunde Salako, Naoharu Iwai, Yoshikuni Kita, Toshio Ogihara, Takayoshi Ohkubo, Tomonori Okamura, Hirotsugu Ueshima, Satoshi Umemura, Susana Eyheramendy, H.-Erich Wichmann, Yoon Shin Cho, Hyung-Lae Kim, Jong-Young Lee, James Scott, Joban S. Sehmi, Weihua Zhang, Bo Hedblad, Peter Nilsson, George Davey Smith, Andrew Wong, Narisu Narisu, Alena Stančáková, Leslie J. Raffel, Jie Yao, Sekar Kathiresan, Chris O’Donnell, Stephen M. Schwartz, M. Arfan Ikram, W.T. Longstreth, Thomas H. Mosley, Sudha Seshadri, Nick R.G. Shrine, Louise V. Wain, Mario A. Morken, Amy J. Swift, Jaana Laitinen, Inga Prokopenko, Paavo Zitting, Jackie A. Cooper, Steve E. Humphries, John Danesh, Asif Rasheed, Anuj Goel, Anders Hamsten, Hugh Watkins, Stephan J.L. Bakker, Wiek H. van Gilst, Charles S. Janipalli, K. RadhaMani, Chittaranjan S. Yajnik, Francesco U.S. Mattace-Raso, Ben A. Oostra, Ayse Demirkan, Aaron Isaacs, Fernando Rivadeneira, Edward G. Lakatta, Marco Orru, Angelo Scuteri, Mika Ala-Korpela, Antti J. Kangas, Leo-Pekka Lyytikäinen, Pasi Soininen, Taru Tukiainen, Peter Würtz, Rick Twee-Hee Ong, Heyo K. Kroemer, Henry Völzke, Pilar Galan, Serge Hercberg, Mark Lathrop, Diana Zelenika, Panos Deloukas, Massimo Mangino, Tim D. Spector, Guangju Zhai, James F. Meschia, Michael A. Nalls, Pankaj Sharma, Janos Terzic, M.J. Kranthi Kumar, Matthew Denniff, Ewa Zukowska-Szczechowska, Lynne E. Wagenknecht, F. Gerald R. Fowkes, Fadi J. Charchar, Peter E.H. Schwarz, Caroline Hayward, Xiuqing Guo, Charles Rotimi, Michiel L. Bots, Eva Brand, Nilesh J. Samani, Ozren Polasek, Philippa J. Talmud, Fredrik Nyberg, Diana Kuh, Maris Laan, Kristian Hveem, Lyle J. Palmer, Yvonne T. van der Schouw, Juan P. Casas, Karen L. Mohlke, Paolo Vineis, Olli Raitakari, Santhi K. Ganesh, Tien Y. Wong, E. Shyong Tai, Richard S. Cooper, Markku Laakso, Dabeeru C. Rao, Tamara B. Harris, Richard W. Morris, Anna F. Dominiczak, Mika Kivimaki, Tetsuro Miki, Danish Saleheen, Giriraj R. Chandak, Veikko Salomaa, Bok-Ghee Han, Xiaofeng Zhu, Jaspal S. Kooner, Olle Melander, Paul M. Ridker, Ulf B. Gyllensten, Alan F. Wright, James F. Wilson, Josef Coresh, Martin Farrall, Peter P. Pramstaller, Roberto Elosua, Nicole Soranzo, Eric J.G. Sijbrands, David Altshuler, Ruth J.F. Loos, Alan R. Shuldiner, Christian Gieger, Nicholas J. Wareham, Vilmundur Gudnason, Jerome I. Rotter, Manuela Uda, David P. Strachan, Jacqueline C.M. Witteman, Martin G. Larson, Marjo-Riitta Järvelin, Bruce M. Psaty, Gonçalo R. Abecasis, Aravinda Chakravarti, Paul Elliott, Cornelia M. van Duijn, Christopher Newton-Cheh, Mark J. Caulfield, Toby Johnson, Anna-Liisa Hartikainen, Eric Boerwinkle
Genome-wide association studies (GWAS) have uncovered numerous genetic variants (SNPs) that are associated with blood pressure (BP). Genetic variants may lead to BP changes by acting on intermediate molecular phenotypes such as coded protein sequence or gene expression, which in turn affect BP variability. Therefore, characterizing genes whose expression is associated with BP may reveal cellular processes involved in BP regulation and uncover how transcripts mediate genetic and environmental effects on BP variability. A meta-analysis of results from six studies of global gene expression profiles of BP and hypertension in whole blood was performed in 7017 individuals who were not receiving antihypertensive drug treatment. We identified 34 genes that were differentially expressed in relation to BP (Bonferroni-corrected p<0.05). Among these genes, FOS and PTGS2 have been previously reported to be involved in BP-related processes; the others are novel. The top BP signature genes in aggregate explain 5%–9% of inter-individual variance in BP. Of note, rs3184504 in SH2B3, which was also reported in GWAS to be associated with BP, was found to be a trans regulator of the expression of 6 of the transcripts we found to be associated with BP (FOS, MYADM, PP1R15A, TAGAP, S100A10, and FGBP2). Gene set enrichment analysis suggested that the BP-related global gene expression changes include genes involved in inflammatory response and apoptosis pathways. Our study provides new insights into molecular mechanisms underlying BP regulation, and suggests novel transcriptomic markers for the treatment and prevention of hypertension.
The National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, MA, United States; The Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Bethesda, MD, United States; Estonian Genome Center, University of Tartu, Tartu, Estonia; Division of Endocrinology, Children’s Hospital Boston, Boston, MA, United States; Department of Genetics, Harvard Medical School, Boston, MA, United States; Broad Institute of Harvard and MIT, Cambridge, MA, United States; Department of Internal Medicine, Erasmus Medical Centre Rotterdam, Rotterdam, Netherlands; Netherlands Genomics Initiative–sponsored Netherlands Consortium for Healthy Aging (NGI‐NCHA), Leiden and Rotterdam, Netherlands; Epidemiology and Public Health Group, Medical School, University of Exeter, Exeter, United Kingdom; Institute of Human Genetics, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, München, Germany; Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany; The Charles Bronfman Institute for Personalized Medicine, Genetics of Obesity & Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY, United States; Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, MD, United States; Harvard Medical School, Boston, MA, United States; Hebrew SeniorLife, Boston, Boston, Massachusetts, United States; Cardiovascular Epidemiology and Human Genomics Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Bethesda, MD, United States; Division of Geriatrics and Clinical Gerontology National Institute on Aging, Bethesda, MD, United States; Genomics Core facility Genetics & Developmental Biology Center, National Heart, Lung, and Blood Institute, Bethesda, MD, United States; Department of Epidemiology, Erasmus Medical Centre Rotterdam, Rotterdam, Netherlands; Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, United States; Geriatric Unit, Azienda Sanitaria Firenze, Florence, Italy; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany; German Center for Diabetes Research (DZD e.V.), Partner Düsseldorf, Düsseldorf, Germany; Research Unit of Molecular Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany; Institute of Epidemiology II, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany; German Center for Diabetes Research (DZD e.V.), Partner Munich, Munich, Germany; DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany; Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany; University Medicine Greifswald, Department of Internal Medicine B—Cardiology, Greifswald, Germany; DZHK (German Center for Cardiovascular Research), partner site Greifswald, Greifswald, Germany; Universitäres Herzzentrum Hamburg, Hamburg, Germany; DZHK (German Centre for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Hamburg, Germany; Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, United States; Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States; Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, 21205, MD, United States; Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois and University of Lausanne, Bugnon 17, Lausanne, 1005, Switzerland; Cardiology, Department of Specialties of Internal Medicine, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, Geneva 14, 1211, Switzerland; Clinical Pharmacology and The Genome Centre, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, United Kingdom; Department of Biostatistics, University of Washington, Seattle, WA, United States; Framingham Heart Study, Framingham, MA, United States; National Heart Lung, and Blood Institute, Bethesda, MD, United States; Division of Preventive Medicine, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, 02215, MA, United States; Harvard Medical School, Boston, MA, United States; Icelandic Heart Association, Kopavogur, Iceland; University of Iceland, Reykajvik, Iceland; Department of Health Sciences, University of Leicester, University Rd, Leicester, LE1 7RH, United Kingdom; Department of Epidemiology, Erasmus Medical Center, PO Box 2040, Rotterdam, 3000 CA, Netherlands; Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands; Netherlands Consortium for Healthy Aging (NCHA), Netherland Genome Initiative (NGI), Netherlands; Center for Population Studies, National Heart Lung, and Blood Institute, Bethesda, MD, United States; Department of Internal Medicine, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, United Kingdom; Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, 48103, MI, United States; Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Greifswald, 17487, Germany; Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA, United States; Laboratory of Epidemiology, Demography, Biometry, National Institute on Aging, National Institutes of Health, Bethesda, 20892, Maryland, United States; MRC Epidemiology Unit, Institute of Metabolic Science, Cambridge, CB2 0QQ, United Kingdom; Centre National de Génotypage, Commissariat à L'Energie Atomique, Institut de Génomique, Evry, France; Institute of Molecular and Cell Biology, University of Tartu, Riia 23, Tartu, 51010, Estonia; University of Maryland School of Medicine, Baltimore, 21201, MD, USA, United States; Center for Human Genetic Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, 02114, MA, United States; Department of Twin Research & Genetic Epidemiology, King's College London, United Kingdom; Cardiovascular Epidemiology and Genetics, Institut Municipal d'Investigacio Medica, Barcelona Biomedical Research Park, 88 Doctor Aiguader, Barcelona, 08003, Spain; Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Viale Druso 1, Bolzano, 39100, Italy; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, Michigan, United States; Department of Cardiovascular Medicine, The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, United Kingdom; Clinical Research Branch, National Institute on Aging, Baltimore, 21250, MD, United States; Centre for Population Health Sciences, University of Edinburgh, EH89AG, United Kingdom; Centre for Population Health Sciences and Institute of Genetics and Molecular Medicine, College of Medicine and Vet Medicine, University of Edinburgh, EH8 9AG, United Kingdom; Croatian Centre for Global Health, University of Split, Croatia; Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, SE-751 85, Sweden; Amgen, 1 Kendall Square, Building 100, Cambridge, 02139, MA, United States; Department of Clinical Sciences, Lund University, Malmö, Sweden; Department of Medicine, University of Verona, Italy; Ealing Hospital, London, UB1 3HJ, United Kingdom; Department of Medicine, University of Mississippi Medical Center, United States; Genetic Epidemiology Group, Epidemiology and Public Health, UCL, London, WC1E 6BT, United Kingdom; Center for Genome Science, National Institute of Health, Seoul, South Korea; Department of Cardiology, University Medical Center Groningen, University of Groningen, Netherlands; Departments of Epidemiology and Medicine, Johns Hopkins University, Baltimore MD, United States; Centre for Cellular and Molecular Biology (CCMB), Council of Scientific and Industrial Research (CSIR), Uppal Road, 500 007, Hyderabad, India; Department of Public Health and Primary Care, University of Cambridge, CB1 8RN, United Kingdom; Department of Basic Medical Research and Education, and Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, 791-0295, Japan; Division of Community Health Sciences, St George's University of London, London, SW17 0RE, United Kingdom; Epidemiology & Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, 27157, NC, United States; Division of Biostatistics and Department of Genetics, School of Medicine, Washington University in St. Louis, Saint Louis, 63110, MO, United States; Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, 70210, Finland; Department of Preventive Medicine and Epidemiology, Loyola University Medical School, Maywood, IL, United States; Department of Laboratory Medicine & Institute of Human Genetics, University of California San Francisco, 513 Parnassus Ave., San Francisco, 94143, CA, United States; Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, 138672, Singapore; Centre for Molecular Epidemiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117597, Singapore; Department of Clinical Chemistry, University of Tampere and Tampere University Hospital, Tampere, 33521, Finland; Department of Genetics, Biology and Biochemistry, University of Torino, Via Santena 19, Torino, 10126, Italy; Human Genetics Foundation (HUGEF), Via Nizza 52, Torino, 10126, Italy; Department of Genetics, University of North Carolina, Chapel Hill, 27599, NC, United States; MRC Centre for Causal Analyses in Translational Epidemiology, School of Social & Community Medicine, University of Bristol, Bristol, BS8 2BN, United Kingdom; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, GA Utrecht, 3508, Netherlands; Complex Genetics Section, Department of Medical Genetics—DBG, University Medical Center Utrecht, GA Utrecht, 3508, Netherlands; Centre for Genetic Epidemiology and Biostatistics, University of Western Australia, Crawley, WA, Australia; HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, 7600 Levanger, Norway; MRC Unit for Lifelong Health & Ageing, London, WC1B 5JU, United Kingdom; Occupational and Environmental Medicine, Department of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 40530, Sweden; Centre for Cardiovascular Genetics, University College London, London, WC1E 6JF, United Kingdom; MRC Human Genetics Unit and Institute of Genetics and Molecular Medicine, Edinburgh, EH2, United Kingdom; Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom; Leicester NIHR Biomedical Research Unit in Cardiovascular Disease, Glenfield Hospital, Leicester, LE3 9QP, United Kingdom; Studies Coordinating Centre, Division of Hypertension and Cardiac Rehabilitation, Department of Cardiovascular Diseases, University of Leuven, Campus Sint Rafaël, Kapucijnenvoer 35, Block D, Box 7001, Leuven, 3000, Belgium; Center for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, 20892, MD, United States; Columbia University, NY, United States; Department of Medicine III, Medical Faculty Carl Gustav Carus at the Technical University of Dresden, Dresden, 01307, Germany; Epidemiology and Biostatistics, School of Public Health, Imperial College, London, W2 1PG, United Kingdom; Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece; Wake Forest University Health Sciences, Winston-Salem, 27157, NC, United States; Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, 48109, MI, United States; Division of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas at Houston Health Science Center, 12 Herman Pressler, Suite 453E, Houston, 77030, TX, United States; Laboratory of Neurogenetics, National Institute on Aging, Bethesda, 20892, MD, United States; Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH, Baltimore, Maryland, United States; Washington Hospital Center, Division of Cardiology, Washington, DC, United States; ALSPAC Laboratory, University of Bristol, Bristol, BS8 2BN, United Kingdom; Pediatric Epidemiology Center, University of South Florida, Tampa, FL, United States; Clinical Pharmacology Unit, University of Cambridge, Addenbrookes Hospital, Hills Road, Cambridge, CB2 2QQ, United Kingdom; University of Dundee, Ninewells Hospital &Medical School, Dundee, DD1 9SY, United Kingdom; Genetic Epidemiology Group, Department of Epidemiology and Public Health, UCL, London, WC1E 6BT, United Kingdom; Pathology and Laboratory Medicine, University of Western Australia, Crawley, WA, Australia; Molecular Genetics, PathWest Laboratory Medicine, Nedlands, WA, Australia; Clinical Trial Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, OX3 7LF, United Kingdom; Department of Epidemiology and Biostatistics, Case Western Reserve University, 2103 Cornell Road, Cleveland, 44106, OH, United States; Department of Medicine, Johns Hopkins University, Baltimore, United States; Department of Clinical Physiology, University of Tampere and Tampere University Hospital, Tampere, 33521, Finland; Department of Medicine, University of Turku and Turku University Hospital, Turku, 20521, Finland; Department of Nutrition, University of North Carolina, Chapel Hill, 27599, NC, United States; Office of Population Studies Foundation, University of San Carlos, Talamban, Cebu City, 6000, Philippines; Department of Neurology and Framingham Heart Study, Boston University School of Medicine, Boston, 02118, MA, United States; Department of Internal Medicine II, University Medical Center Regensburg, Regensburg, 93053, Germany; Department of Epidemiology and Preventive Medicine, University Medical Center Regensburg, Regensburg, 93053, Germany; Department of Epidemiology, Johns Hopkins University, Baltimore, MD, United States; Renal Division, University Hospital Freiburg, Germany; Département de Génétique Médicale, Université de Lausanne, Lausanne, 1015, Switzerland; Swiss Institute of Bioinformatics, Lausanne, 1015, Switzerland; Division of Genetics, GlaxoSmithKline, Philadelphia, 19101, PA, United States; International Centre for Circulatory Health, National Heart & Lung Institute, Imperial College, London, United Kingdom; Genetics of Complex Traits, Peninsula Medical School, University of Exeter, United Kingdom; Department of Community Health Sciences & Department of Medicine, Aga Khan University, Karachi, Pakistan; Medizinische Klinik II, Universität zu Lübeck, Lübeck, Germany; Diabetes Unit, KEM Hospital and Research Centre, Rasta Peth, Pune, Maharashtra, 411011, India; Department of Clinical Sciences, Diabetes and Endocrinology Research Unit, University Hospital, Malmö, Sweden; Lund University, Malmö, 20502, Sweden; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, 02139, MA, United States; Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, FIN-00251, Finland; William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, EC1M 6BQ, United Kingdom; Merck Research Laboratory, 126 East Lincoln Avenue, Rahway, 07065, NJ, United States; Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, United Kingdom; University of Cambridge Metabolic Research Labs, Institute of Metabolic Science Addenbrooke's Hospital, Cambridge, CB2 OQQ, United Kingdom; Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States; Cardiovascular Genetics, University of Utah School of Medicine, Salt Lake City, UT, United States; Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, 90033, CA, United States; National Human Genome Research Institute, National Institutes of Health, Bethesda, 20892, MD, United States; National Institute for Health and Welfare, Helsinki, 00271, Finland; FIMM, Institute for Molecular Medicine, Finland, Biomedicum, P.O. Box 104, Helsinki, 00251, Finland; Broad Institute, Cambridge, 02142, MA, United States; Leibniz-Institute for Arteriosclerosis Research, Department of Molecular Genetics of Cardiovascular Disease, University of Münster, Münster, Germany; Medical Faculty of the Westfalian Wilhelms University Muenster, Department of Molecular Genetics of Cardiovascular Disease, University of Muenster, Muenster, Germany; Division of Cardiology, Massachusetts General Hospital, Boston, MA, United States; Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, GA, United States; Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands; Department of Biostatical Sciences, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, 27157, NC, United States; Department of Epidemiology, University of Washington, Seattle, 98195, WA, United States; Group Health Research Institute, Group Health Cooperative, Seattle, WA, United States; Seattle Epidemiologic Research and Information Center, Veterans Health Administration Office of Research & Development, Seattle, 98108, WA, United States; Department of Medicine, University of Washington, 98195, United States; Department of Cardiology, University of Tartu, L. Puusepa 8, Tartu, 51014, Estonia; Tallinn University of Technology, Institute of Biomedical Engineering, Ehitajate tee 5, Tallinn, 19086, Estonia; Centre of Cardiology, North Estonia Medical Centre, Sütiste tee 19, Tallinn, 13419, Estonia; Division of Non-communicable disease Epidemiology, The London School of Hygiene and Tropical Medicine London, Keppel Street, London, WC1E 7HT, United Kingdom; South Asia Network for Chronic Disease, Public Health Foundation of India, C-1/52, SDA, New Delhi, 100016, India; Department of Emergency and Cardiovascular Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, 41685, Sweden; Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, 0317, Norway; Tuscany Regional Health Agency, Florence, Italy; Tropical Medicine Research Institute, University of the West Indies, Mona, Kingston, Jamaica; University of Ibadan, Ibadan, Nigeria; Department of Genomic Medicine, and Department of Preventive Cardiology, National Cerebral and Cardiovascular Research Center, Suita, 565-8565, Japan; Department of Health Science, Shiga University of Medical Science, Otsu, 520-2192, Japan; Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan; Tohoku University Graduate School of Pharmaceutical Sciences and Medicine, Sendai, 980-8578, Japan; Lifestyle-related Disease Prevention Center, Shiga University of Medical Science, Otsu, 520-2192, Japan; Department of Medical Science and Cardiorenal Medicine, Yokohama City University School of Medicine, Yokohama, 236-0004, Japan; Department of Statistics, Pontificia Universidad Catolica de Chile, Vicuña Mackena, Santiago, 4860, Chile; Institute of Human Genetics, Helmholtz Zentrum Munich, German Research Centre for Environmental Health, Neuherberg, 85764, Germany; Institute of Human Genetics, Klinikum rechts der Isar, Technical University of Munich, Munich, 81675, Germany; Institute of Epidemiology, Helmholtz Zentrum Munich, German Research Centre for Environmental Health, Neuherberg, 85764, Germany; Chair of Epidemiology, Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, 81377, Germany; Klinikum Grosshadern, Munich, 81377, Germany; National Heart and Lung Institute, Imperial College London, London, UK, W12 0HS, United Kingdom; Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States; Medical Population Genetics, Broad Institute of Harvard and MIT, 5 Cambridge Center, Cambridge, 02142, MA, United States; National Heart, Lung and Blood Institute and its Framingham Heart Study, 73 Mount Wayte Ave., Suite #2, Framingham, 01702, MA, United States; Department of Neurology and Medicine, University of Washington, Seattle, United States; Department of Medicine (Geriatrics), University of Mississippi Medical Center, Jackson, MS, United States; Department of Neurology, Boston University School of Medicine, United States; Finnish Institute of Occupational Health, Finnish Institute of Occupational Health, Aapistie 1, Oulu, 90220, Finland; Wellcome Trust Centre for Human Genetics, University of Oxford, United Kingdom; Lapland Central Hospital, Department of Physiatrics, Box 8041, Rovaniemi, 96101, Finland; Center for Non-Communicable Diseases Karachi, Pakistan; Atherosclerosis Research Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden; Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Netherlands; Department of Medical Genetics, Erasmus Medical Center, Rotterdam, Netherlands; Gerontology Research Center, National Institute on Aging, Baltimore, 21224, MD, United States; Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Cittadella Universitaria di Monserrato, Monserrato, Cagliari, Italy; Unita`Operativa Semplice Cardiologia, Divisione di Medicina, Presidio Ospedaliero Santa Barbara, Iglesias, Italy; Computational Medicine Research Group, Institute of Clinical Medicine, University of Oulu and Biocenter Oulu, 90014 University of Oulu, Oulu, Finland; NMR Metabonomics Laboratory, Department of Biosciences, University of Eastern Finland, Kuopio, 70211, Finland; Department of Internal Medicine and Biocenter Oulu, Clinical Research Center, 90014 University of Oulu, Oulu, Finland; Institute for Molecular Medicine Finland FIMM, 00014 University of Helsinki, Helsinki, Finland; Department of Biomedical Engineering and Computational Science, School of Science and Technology, Aalto University, Aalto, Espoo, 00076, Finland; NUS Graduate School for Integrative Sciences & Engineering (NGS) Centre for Life Sciences (CeLS), Singapore, 117456, Singapore; Department of Internal Medicine B, Ernst-Moritz-Arndt-University Greifswald, Greifswald, 17487, Germany; Institute of Pharmacology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, 17487, Germany; Institute for Community Medicine, Ernst-Moritz-Arndt-University Greifswald, Greifswald, 17487, Germany; U557 Institut National de la Santé et de la Recherche Médicale, U1125 Institut National de la Recherche Agronomique, Université Paris 13, Bobigny, France; Department of Neurology, Mayo Clinic, Jacksonville, FL, United States; Imperial College Cerebrovascular Unit (ICCRU), Imperial College, London, W6 8RF, United Kingdom; Faculty of Medicine, University of Split, Croatia; Department of Internal Medicine, Diabetology, and Nephrology, Medical University of Silesia, Zabrze, 41-800, Poland; Public Health Sciences section, Division of Community Health Sciences, University of Edinburgh, Medical School, Teviot Place, EH8 9AG, Edinburgh, United Kingdom; School of Science and Engineering, University of Ballarat, Ballarat, 3353, Australia; Prevention and Care of Diabetes, Department of Medicine III, Medical Faculty Carl Gustav Carus at the Technical University of Dresden, Dresden, 01307, Germany; University Hospital Münster, Internal Medicine D, Münster, Germany; Department of Medical Statistics, Epidemiology and Medical Informatics, Andrija Stampar School of Public Health, University of Zagreb, Croatia; AstraZeneca R&D, Mölndal, 431 83, Sweden; Genetic Epidemiology & Biostatistics Platform, Ontario Institute for Cancer Research, Toronto, Canada; Samuel Lunenfeld Institute for Medical Research, University of Toronto, Canada; Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, United Kingdom; Department of Epidemiology and Public Health, Imperial College, Norfolk Place, London, W2 1PG, United Kingdom; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku and the Department of Clinical Physiology, Turku University Hospital, Turku, 20521, Finland; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan Medical Center, Ann Arbor, Michigan, United States; Singapore Eye Research Institute, Singapore, 168751, Singapore; Department of Ophthalmology, National University of Singapore, Singapore, 119074, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 119074, Singapore; Duke-National University of Singapore Graduate Medical School, Singapore, 169857, Singapore; Division of Biostatistics, Washington University School of Medicine, Saint Louis, 63110, MO, United States; Department of Primary Care & Population Health, UCL, London, NW3 2PF, United Kingdom; BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, United Kingdom; Epidemiology Public Health, UCL, London, WC1E 6BT, United Kingdom; Departments of Epidemiology, Biostatistics, and Medicine, Johns Hopkins University, Baltimore, MD, United States; Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Netherlands; Division of Cardiology, Brigham and Women's Hospital, 900 Commonwealth Avenue East, Boston, 02215, MA, United States; Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy; National Institute for Health and Welfare, Diabetes Prevention Unit, Helsinki, 00271, Finland; Hjelt Institute, Department of Public Health, University of Helsinki, Helsinki, 00014, Finland; South Ostrobothnia Central Hospital, Seinäjoki, 60220, Finland; Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, Madrid, 28046, Spain; Department of Neurology, General Central Hospital, Bolzano, 39100, Italy; CIBER Epidemiología y Salud Pública, Barcelona, 08003, Spain; Department of Medicine and Department of Genetics, Harvard Medical School, Boston, 02115, MA, United States; Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, MD, United States; U872 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, Paris, France; Institute of Physiology, Ernst-Moritz-Arndt-University Greifswald, Greifswald, 17487, Germany; Institute of Clinical Medicine/Obstetrics and Gynecology, University of Oulu, Finland; Service of Medical Genetics, Centre Hospitalier Universitaire Vaudois, Lausanne, 1011, Switzerland; Human Genetics Center, 1200 Hermann Pressler, Suite E447, Houston, 77030, TX, United States; Division of Epidemiology and Prevention, Boston University School of Medicine, Boston, MA, United States; Department of Mathematics, Boston University, Boston, MA, United States; Institute of Health Sciences, University of Oulu, BOX 5000, University of Oulu, 90014, Finland; Biocenter Oulu, University of Oulu, BOX 5000, University of Oulu, 90014, Finland; National Institute for Health and Welfare, Box 310, Oulu, 90101, Finland; MRC-HPA Centre for Environment and Health, School of Public Health, Imperial College London, Norfolk Place, London, W2 1PG, United Kingdom; Centre of Medical Systems Biology (CMSB 1–2), NGI Erasmus Medical Center, Rotterdam, Netherlands; Institute of the University of Lübeck, Germany
