Article abstract
Nature Genetics 41, 677 - 687 (2009)
Published online: 10 May 2009 | Corrected online: 17 May 2009 | doi:10.1038/ng.384
Genome-wide association study of blood pressure and hypertension
Daniel Levy1,2,29, Georg B Ehret3,4,29, Kenneth Rice5,29, Germaine C Verwoert6,7,28,29, Lenore J Launer8,29, Abbas Dehghan6, Nicole L Glazer9, Alanna C Morrison10, Andrew D Johnson1,2, Thor Aspelund11,12, Yurii Aulchenko6, Thomas Lumley5, Anna Köttgen13, Ramachandran S Vasan1,14,15,16,17, Fernando Rivadeneira6,7, Gudny Eiriksdottir11, Xiuqing Guo18, Dan E Arking3, Gary F Mitchell19, Francesco U S Mattace-Raso6,20, Albert V Smith11, Kent Taylor18, Robert B Scharpf21, Shih-Jen Hwang1,2, Eric J G Sijbrands7, Joshua Bis9, Tamara B Harris8, Santhi K Ganesh3,22, Christopher J O'Donnell1,2, Albert Hofman6, Jerome I Rotter18, Josef Coresh13, Emelia J Benjamin1,14,15,16,17, André G Uitterlinden6,7, Gerardo Heiss23, Caroline S Fox1,2, Jacqueline C M Witteman6,28, Eric Boerwinkle10, Thomas J Wang1,24, Vilmundur Gudnason11,12,29, Martin G Larson1,25,29, Aravinda Chakravarti3,13,29, Bruce M Psaty26,27,29 & Cornelia M van Duijn6,29
Abstract
Blood pressure is a major cardiovascular disease risk factor. To date, few variants associated with interindividual blood pressure variation have been identified and replicated. Here we report results of a genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium (n = 29,136), identifying 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P < 4 
10-7. The top ten loci for SBP and DBP were incorporated into a risk score; mean BP and prevalence of hypertension increased in relation to the number of risk alleles carried. When ten CHARGE SNPs for each trait were included in a joint meta-analysis with the Global BPgen Consortium (n = 34,433), four CHARGE loci attained genome-wide significance (P < 5 10-8) for SBP (ATP2B1, CYP17A1, PLEKHA7, SH2B3), six for DBP (ATP2B1, CACNB2, CSK-ULK3, SH2B3, TBX3-TBX5, ULK4) and one for hypertension (ATP2B1). Identifying genes associated with blood pressure advances our understanding of blood pressure regulation and highlights potential drug targets for the prevention or treatment of hypertension.
- National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
- Center for Population Studies, NHLBI, Bethesda, Maryland, USA.
- McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
- Division of Cardiology, Geneva University Hospital, Geneva, Switzerland.
- Department of Biostatistics, University of Washington, Seattle, Washington, USA.
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
- Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
- National Institute of Aging's Laboratory for Epidemiology, Demography, and Biometry, Bethesda, Maryland, USA.
- Cardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, Washington, USA.
- Human Genetics Center, University of Texas Health Science Center, Houston, Texas, USA.
- Icelandic Heart Association, Kopavogur, Iceland.
- University of Iceland, Reykjavik, Iceland.
- Department of Epidemiology and Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
- Department of Cardiology, Boston University School of Medicine, Boston, Massachusetts, USA.
- Department of Preventive Medicine, Boston University School of Medicine, Boston, Massachusetts, USA.
- Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts, USA.
- Epidemiology Section, Boston University School of Public Health, Boston, Massachusetts, USA.
- Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
- Cardiovascular Engineering, Inc., Norwood, Massachusetts, USA.
- Department of Internal Medicine, Section of Geriatric Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
- Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland, USA.
- National Human Genome Research Institute, Vascular Biology Section, Bethesda, Maryland, USA.
- Carolina Cardiovascular Biology Center, Chapel Hill, North Carolina, USA.
- Division of Cardiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
- Department of Mathematics and Statistics, Boston University, Boston, Massachusetts, USA.
- Departments of Epidemiology, Medicine, and Health Services, University of Washington, Seattle, Washington, USA.
- Center for Health Studies, Group Health, Seattle, Washington, USA.
- Member of the Netherlands Consortium on Healthy Aging (NCHA), The Netherlands.
- These authors contributed equally to this work.
Correspondence to: Daniel Levy1,2,29 e-mail: levyd@nhlbi.nih.gov
Correspondence to: Cornelia M van Duijn6,29 e-mail: c.vanduijn@erasmusmc.nl
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