Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10−24), CYP1A2 (P = 1 × 10−23), FGF5 (P = 1 × 10−21), SH2B3 (P = 3 × 10−18), MTHFR (P = 2 × 10−13), c10orf107 (P = 1 × 10−9), ZNF652 (P = 5 × 10−9) and PLCD3 (P = 1 × 10−8) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
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The authors would like to thank the many colleagues who contributed to collection and phenotypic characterization of the clinical samples, as well as genotyping and analysis of the GWA data. They would also especially like to thank those who agreed to participate in the studies. Major funding for the work described in the paper comes from the following (alphabetically): Academy of Finland (124243, 129322, 129494, 118065), AGAUR (SGR 2005/00577), Albert Påhlsson Research Foundation, Alexander-von-Humboldt Foundation (V-Fokoop-1113183), American Diabetes Association, AstraZeneca AB, AVIS Torino blood donor organization, Barts and The London Charity, Biocenter of University of Oulu, Board of the UMC Utrecht, British Heart Foundation (PG02/128, FS/05/061/19501, SP/04/002), Burroughs Wellcome Fund, CamStrad, Cancer Research United Kingdom, CIBER Epidemiología y Salud Pública, Commissariat à l'Energie Atomique, Compagnia di San Paolo to the ISI Foundation (Torino, Italy), Conservatoire National des Arts et Métiers, Crafoord Foundation, Donovan Family Foundation, Doris Duke Charitable Foundation, Dutch Kidney Foundation (E033), Dutch College of Healthcare Insurance Companies, Dutch Ministry of Health, Dutch Organisation of Health Care Research, ENGAGE (HEALTH-F4-2007-201413), Ernhold Lundströms Research Foundation, Estonian Ministry of Education and Science (0182721s06), EURO-BLCS, European Commission (QLG1-CT-2000-01643, LSHM-CT-2007-037273), European Commission-Europe Against Cancer (AEP/90/05), European Union (FP-6 LSHM-CT-2003-503041, FP-6 LSHM CT 2006 037697), European Society for the Study of Diabetes, Faculty of Biology and Medicine of Lausanne, Switzerland, Fannie E. Rippel Foundation, Finnish Foundation for Cardiovascular Research, FIS (CP05/00290), Fundació Marató Tv3, German Federal Ministry of Education and Research (01ZZ9603, 01ZZ0103, 01ZZ0403, 03ZIK012, 01EZ0874), German National Genome Research Network, German Research Center for Environmental Health, (Neuherberg, Germany), Giorgi-Cavaglieri Foundation, GlaxoSmithKline, Guy's & St. Thomas' NHS Foundation Trust, Health Research and Development Council of the Netherlands (2100.0008, 2100.0042), Helmholtz Zentrum München, Hulda and Conrad Mossfelt Foundation, Institut National de la Recherche Agronomique, Institut National de la Santé et de la Recherche Médicale, Italian Association for Research on Cancer, Italian Ministry of Health (110.1RS97.71), Italian National Research Council, Juvenile Diabetes Research Fund, King Gustaf V and Queen Victoria Foundation, King's College London and King's College Hospital NHS Foundation Trust, Knut and Alice Wallenberg Foundation, Lennart Hanssons Memorial Fund, LK Research Funds, Massachusetts General Hospital Cardiovascular Research Center and Department of Medicine, Medical Faculty of Lund University and Malmö University Hospital, Medical Research Council of the UK (G0000934, G0501942, G9521010D), Medical Research Council-GlaxoSmithKline (85374), MedStar Research Institute, Ministerio de Sanidad y Consumo, Instituto de Salud Carlos III (RD06/0009, CP05/290, PI061254, CIBERESP), Ministry of Cultural Affairs and Social Ministry (Federal State of Mecklenburg-West Pomerania), National Institute for Health Research (NIHR), National Institute for Health Research Cambridge Biomedical Research Centre, Novartis Institute for Biomedical Research, NWO VENI (916.76.170), Province of Utrecht, Region Skane, Siemens Healthcare (Erlangen, Germany), Sigrid Juselius Foundation, Stockholm County Council (562183), Support for Science Funding programme, Swedish Heart and Lung Foundation, Swedish Medical Research Council, Swedish National Research Council, Swedish Research Council (8691), Swiss National Science Foundation (33CSO-122661, 310030-112552, 3100AO-116323/1, PROSPER 3200BO-111362/1, 3233BO-111361/1), UNIL, University of Utrecht, US National Institutes of Health (U01DK062418, K23HL80025, DK062370, DK072193, U54DA021519, 1Z01HG000024, N01AG-916413, N01AG-821336, 263MD916413, 263MD821336, Intramural NIA, R01HL087676, K23HL083102, U54RR020278, R01HL056931, P30ES007033, R01HL087679, RL1MH083268, 263-MA-410953, NO1-AG-1-2109, N01-HD-1-3107), WCRF (98A04, 2000/30), Wellcome Trust (068545/Z/02, 076113/B/04/Z, 079895, 070191/Z/03/Z, 077016/Z/05/Z, WT088885/Z/09/Z).
Supplementary Figures 1 and 2, Supplementary Tables 1–4, Supplementary Methods and Supplementary Note