Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

Affiliations

• ¹ Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
• ² Institute of Health Sciences, University of Oulu, Oulu, Finland.
• ³ Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
• ⁴ Translational Laboratory in Genetic Medicine, Agency for Science, Technology and Research (ASTAR), Singapore.
• ⁵ Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
• ⁶ Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore.
• ⁷ Ealing Hospital National Health Service (NHS) Trust, Middlesex, UK.
• ⁸ Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, USA.
• ⁹ Center for Non-Communicable Diseases, Karachi, Pakistan.
• ¹⁰ Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK.
• ¹¹ Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
• ¹² Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
• ¹³ Bioinformatics Support Service, Imperial College London, London, UK.
• ¹⁴ Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
• ¹⁵ German Center for Diabetes Research (DZD), Neuherberg, Germany.
• ¹⁶ National Heart and Lung Institute, Imperial College London, London, UK.
• ¹⁷ Novo Nordisk Foundation Centre for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
• ¹⁸ Copenhagen Prospective Studies on Asthma in Childhood (COSPAC), Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
• ¹⁹ Steno Diabetes Center, Gentofte, Denmark.
• ²⁰ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
• ²¹ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
• ²² Vanderbilt Epidemiology Center, Center for Human Genetics Research, Division of Epidemiology, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
• ²³ Estonian Genome Center, University of Tartu, Tartu, Estonia.
• ²⁴ Division of Endocrinology, Children's Hospital Boston, Boston, Massachusetts, USA.
• ²⁵ Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
• ²⁶ Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
• ²⁷ Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Chungcheongbuk-do, Republic of Korea.
• ²⁸ Medical Genetics Section, University of Edinburgh Centre for Genomic and Experimental Medicine and Medical Research Council (MRC) Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK.
• ²⁹ Centre for Cognitive Aging and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
• ³⁰ Department of Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
• ³¹ Institute for Genetic Medicine, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
• ³² Department of Public Health, Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
• ³³ Genome Institute of Singapore, ASTAR, Singapore.
• ³⁴ Department of Ophthalmology, National University of Singapore, Singapore.
• ³⁵ Department of Paediatrics, National University of Singapore, Singapore.
• ³⁶ Medical Clinic V, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
• ³⁷ Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
• ³⁸ Cancer Science Institute of Singapore, National University of Singapore, Singapore.
• ³⁹ Center for Advanced Medicine and Clinical Research, Nagoya University Hospital, Nagoya, Japan.
• ⁴⁰ Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
• ⁴¹ University of Ottawa Heart Institute, Cardiovascular Research Methods Centre, Ottawa, Ontario, Canada.
• ⁴² Ruddy Canadian Cardiovascular Genetics Centre, Ottawa, Ontario, Canada.
• ⁴³ Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
• ⁴⁴ Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
• ⁴⁵ Singapore Institute for Clinical Sciences (SICS), ASTAR, Singapore.
• ⁴⁶ Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
• ⁴⁷ Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
• ⁴⁸ School of Chinese Medicine, China Medical University, Taichung, Taiwan.
• ⁴⁹ State Key Laboratory of Medical Genetics, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
• ⁵⁰ Shanghai Institute of Hypertension, Shanghai, China.
• ⁵¹ Institute of Epidemiology and Biobank popgen, Christian Albrechts University of Kiel, Kiel, Germany.
• ⁵² Department of Epidemiology and Biostatistics, MRC Health Protection Agency (PHE) Centre for Environment and Health, School of Public Health, Imperial College London, London, UK.
• ⁵³ Clinical Trials Support Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
• ⁵⁴ Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Malmö, Sweden.
• ⁵⁵ MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
• ⁵⁶ Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland.
• ⁵⁷ Department of Clinical Chemistry, University of Tampere School of Medicine, Tampere, Finland.
• ⁵⁸ Vietnam National Heart Institute, Bach Mai Hospital, Hanoi, Vietnam.
• ⁵⁹ School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.
• ⁶⁰ Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.
• ⁶¹ Netherlands Consortium for Healthy Ageing, Leiden, the Netherlands.
• ⁶² Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland.
• ⁶³ Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
• ⁶⁴ Department of Public Health Sciences, University of Chicago, Chicago, Illinois, USA.
• ⁶⁵ Institute of Genetics and Biophysics A Buzzati-Traverso, CNR, Naples, Italy.
• ⁶⁶ Division of Heart and Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands.
• ⁶⁷ Division of Genetics and Cell Biology, San Raffaele Scientific Institute, Milan, Italy.
• ⁶⁸ Institute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) 'Burlo Garofolo', Trieste, Italy.
• ⁶⁹ University College London Genetics Institute, Department of Genetics, Environment and Evolution, University College London, London, UK.
• ⁷⁰ Division of Genomics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
• ⁷¹ Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China.
• ⁷² Department of Nutrition, University of North Carolina, Chapel Hill, North Carolina, USA.
• ⁷³ UChicago Research Bangladesh, Uttara, Dhaka, Bangladesh.
• ⁷⁴ Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
• ⁷⁵ Metabolic Disease Group, Wellcome Trust Sanger Institute, Cambridge, UK.
• ⁷⁶ National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
• ⁷⁷ University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK.
• ⁷⁸ Department of Pediatrics, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
• ⁷⁹ Vanderbilt Epidemiology Center, Division of Epidemiology, Department of Medicine, Vanderbilt Genetics Institute, Vanderbilt University, Nashville, Tennessee, USA.
• ⁸⁰ Vanderbilt-Ingram Cancer Center, Division of Epidemiology, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
• ⁸¹ Centre for Quantitative Medicine, Office of Clinical Sciences, Duke-National University of Singapore Graduate Medical School, Singapore.
• ⁸² Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
• ⁸³ Department of Psychology, University of Edinburgh, Edinburgh, UK.
• ⁸⁴ Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
• ⁸⁵ Department of Epidemiology, Shanghai Cancer Institute, Shanghai, China.
• ⁸⁶ Fu Wai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
• ⁸⁷ Dayanand Medical College and Hospital Unit, Hero DMC Heart Institute, Ludhiana, India.
• ⁸⁸ Department of Obstetrics and Gynecology, Oulu University Hospital, Oulu, Finland.
• ⁸⁹ Medical Research Center, University of Oulu, Oulu, Finland.
• ⁹⁰ Unit of Primary Care, Oulu University Hospital, Oulu, Finland.
• ⁹¹ Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio, USA.
• ⁹² Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
• ⁹³ Department of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA.
• ⁹⁴ Department of Paediatrics, Yong Loo Lin School of Medicine, Singapore.
• ⁹⁵ Human Genetics Center, University of Texas School of Public Health at Houston, Houston, Texas, USA.
• ⁹⁶ University of Southern California Keck School of Medicine, Los Angeles, California, USA.
• ⁹⁷ Department of Genetics, Chinese National Human Genomic Center, Shanghai, China.
• ⁹⁸ Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark.
• ⁹⁹ Graduate School of Regional Innovation Studies, Mie University, Tsu, Japan.
• ¹⁰⁰ Department of Geriatric Medicine, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
• ¹⁰¹ Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Suita, Japan.
• ¹⁰² Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Suita, Japan.
• ¹⁰³ National Center for Global Health and Medicine, Toyama, Japan.
• ¹⁰⁴ Duke-National University of Singapore Graduate Medical School, Singapore.
• ¹⁰⁵ Department of Epidemiology and Public Health, University College London, London, UK.
• ¹⁰⁶ K.K. Women's and Children's Hospital, Singapore.
• ¹⁰⁷ University of San Carlos Office of Population Studies Foundation, University of San Carlos, Cebu City, Philippines.
• ¹⁰⁸ Department of Anthropology, Sociology and History, University of San Carlos, Cebu City, Philippines.
• ¹⁰⁹ Department of Internal Medicine, Aichi-Gakuin University School of Dentistry, Nagoya, Japan.
• ¹¹⁰ Institute of Human Genetics, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
• ¹¹¹ Institute of Human Genetics, Technische Universität München, Munich, Germany.
• ¹¹² Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
• ¹¹³ Department of Medicine I, Ludwig Maximilians University Munich, Munich, Germany.
• ¹¹⁴ German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.
• ¹¹⁵ Department of Functional Pathology, Shimane University Faculty of Medicine, Izumo, Japan.
• ¹¹⁶ Division of Endocrinology and Diabetes, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan.
• ¹¹⁷ Department of Diabetes and Endocrinology, Chubu Rosai Hospital, Nagoya, Japan.
• ¹¹⁸ Heart Centre, Department of Cardiology, Tampere University Hospital and University of Tampere School of Medicine, Tampere, Finland.
• ¹¹⁹ Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan.
• ¹²⁰ Department of Geriatric Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
• ¹²¹ MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
• ¹²² Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
• ¹²³ Research and Evaluation Division, Bangladesh Rehabilitation Assistance Committee (BRAC), Dhaka, Bangladesh.
• ¹²⁴ Department of Public Health and Clinical Medicine, Section for Family Medicine, Umeå Universitet, Umeå, Sweden.
• ¹²⁵ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
• ¹²⁶ Department of Vascular Medicine, University Medical Center Utrecht, Utrecht, the Netherlands.
• ¹²⁷ Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
• ¹²⁸ Academic Section of Geriatric Medicine, Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, UK.
• ¹²⁹ Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan.
• ¹³⁰ Institute of Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.
• ¹³¹ Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
• ¹³² Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
• ¹³³ Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland.
• ¹³⁴ Department of Clinical Physiology, University of Tampere School of Medicine, Tampere, Finland.
• ¹³⁵ Department of Health Science, Shiga University of Medical Science, Otsu, Japan.
• ¹³⁶ Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan.
• ¹³⁷ Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
• ¹³⁸ Division of Medicine, Turku University Hospital, Turku, Finland.
• ¹³⁹ Department of Medicine, University of Turku, Turku, Finland.
• ¹⁴⁰ Third Department of Internal Medicine, Shimane University Faculty of Medicine, Izumo, Japan.
• ¹⁴¹ Neuroscience and Behavioural Disorders (NBD) Program, Duke-National University of Singapore Graduate Medical School, Singapore.
• ¹⁴² Duke Eye Center, Duke University Medical Center, Durham, North Carolina, USA.
• ¹⁴³ Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA.
• ¹⁴⁴ Bioinformatics Division, Tsinghua National Laboratory for Informatics Science and Technology (TNLIST), Ministry of Education Key Laboratory of Bioinformatics, Department of Automation, Tsinghua University, Beijing, China.
• ¹⁴⁵ Center for Synthetic and Systems Biology, TNLIST, Ministry of Education Key Laboratory of Bioinformatics, Department of Automation, Tsinghua University, Beijing, China.
• ¹⁴⁶ Department of Psychiatry, University of Hong Kong, Hong Kong.
• ¹⁴⁷ Durrer Center for Cardiogenetic Research, Interuniversity Cardiology Institute of the Netherlands (ICIN)-Netherlands Heart Institute, Utrecht, the Netherlands.
• ¹⁴⁸ Institute of Cardiovascular Science, Faculty of Population Health Sciences, University College London, London, UK.
• ¹⁴⁹ William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
• ¹⁵⁰ King Abdulaziz University, Jeddah, Saudi Arabia.
• ¹⁵¹ Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
• ¹⁵² Institute of Reproductive and Developmental Biology, Imperial College London, Hammersmith Hospital, London, UK.
• ¹⁵³ Hebrew University, School of Public Health, Jerusalem, Israel.
• ¹⁵⁴ School of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
• ¹⁵⁵ Biocenter Oulu, University of Oulu, Oulu, Finland.
• ¹⁵⁶ Center for Life Course Epidemiology, Faculty of Medicine, University of Oulu, Oulu, Finland.
• ¹⁵⁷ ICIN, Utrecht, the Netherlands.
• ¹⁵⁸ Ministry of Health and Welfare, Seoul, Republic of Korea.
• ¹⁵⁹ THERAGEN ETEX Bio Institute, Suwon, Republic of Korea.
• ¹⁶⁰ Department of Clinical Experimental Research, Rigshospitalet, Copenhagen, Denmark.
• ¹⁶¹ Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
• ¹⁶² Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK.
• ¹⁶³ NIHR Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
• ¹⁶⁴ Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.
• ¹⁶⁵ Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Kyushu, Japan.
• ¹⁶⁶ Institute of Molecular Genetics, National Research Council (CNR), Pavia, Italy.
• ¹⁶⁷ Wellcome Trust Sanger Institute, Hinxton, UK.
• ¹⁶⁸ Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
• ¹⁶⁹ Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
• ¹⁷⁰ Synlab Academy, Synlab Services, Mannheim, Germany.
• ¹⁷¹ Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
• ¹⁷² Department of Genome Science, Aichi-Gakuin University School of Dentistry, Nagoya, Japan.
• ¹⁷³ National Hellenic Research Foundation, Institute of Biology, Medicinal Chemistry and Biotechnology, Athens, Greece.
• ¹⁷⁴ Department of Toxicogenomics, Maastricht University, Maastricht, the Netherlands.
• ¹⁷⁵ Oxford Centre for Diabetes Endocrinology and Metabolism, University of Oxford, Oxford, UK.
• ¹⁷⁶ Department of Pathology, National University of Singapore, Singapore.
• ¹⁷⁷ National University of Singapore Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore.
• ¹⁷⁸ Life Sciences Institute, National University of Singapore, Singapore.
• ¹⁷⁹ Department of Statistics and Applied Probability, National University of Singapore, Singapore.
• ¹⁸⁰ Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
• ¹⁸¹ Imperial College Healthcare NHS Trust, London, UK.