Association of Hypertension Drug Target Genes With Blood Pressure and Hypertension in 86 588 Individuals
Year: 2011
Type: article
Abstract: We previously conducted genome-wide association meta-analysis of systolic blood pressure, diastolic blood pressure, and hypertension in 29,136 people from 6 cohort studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Here we examine associations of these traits with 30 gene regions encoding known antihypertensive drug targets. We find nominal evidence of association of ADRB1, ADRB2, AGT, CACNA1A, CACNA1C, and SLC12A3 polymorphisms with 1 or more BP traits in the Cohorts for Heart and Aging Research in Genomic Epidemiology genome-wide association meta-analysis. We attempted replication of the top meta-analysis single nucleotide polymorphisms for these genes in the Global BPgen Consortium (n=34,433) and the Women's Genome Health Study (n=23,019) and found significant results for rs1801253 in ADRB1 (Arg389Gly), with the Gly allele associated with a lower mean systolic blood pressure (β: 0.57 mm Hg; SE: 0.09 mm Hg; meta-analysis: P=4.7×10(-10)), diastolic blood pressure (β: 0.36 mm Hg; SE: 0.06 mm Hg; meta-analysis: P=9.5×10(-10)), and prevalence of hypertension (β: 0.06 mm Hg; SE: 0.02 mm Hg; meta-analysis: P=3.3×10(-4)). Variation in AGT (rs2004776) was associated with systolic blood pressure (β: 0.42 mm Hg; SE: 0.09 mm Hg; meta-analysis: P=3.8×10(-6)), as well as diastolic blood pressure (P=5.0×10(-8)) and hypertension (P=3.7×10(-7)). A polymorphism in ACE (rs4305) showed modest replication of association with increased hypertension (β: 0.06 mm Hg; SE: 0.01 mm Hg; meta-analysis: P=3.0×10(-5)). Two loci, ADRB1 and AGT, contain single nucleotide polymorphisms that reached a genome-wide significance threshold in meta-analysis for the first time. Our findings suggest that these genes warrant further studies of their genetic effects on blood pressure, including pharmacogenetic interactions.
Source: Hypertension
Authors: Andrew D. Johnson, Christopher Newton-Cheh, Daniel I. Chasman, Georg B. Ehret, Toby Johnson, Lynda Rose, Kenneth Rice, Germaine C. Verwoert, Lenore J. Launer, Vilmundur Gudnason, Martin G. Larson, Aravinda Chakravarti, Bruce M. Psaty, Mark Caulfield, Cornelia M. van Duijn, Paul M. Ridker, Patricia B. Munroe, Daniel Levy
Institutions: Broad Institute, Massachusetts General Hospital, National Heart, Lung, and Blood Institute, Framingham Heart Study, Harvard University, University of Geneva, Queen Mary University of London, University of Washington, Leiden University, Erasmus University Rotterdam, University of Iceland, National Institutes of Health, Johns Hopkins University, Group Health Cooperative
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: School of Medicine, Boston University, Cedars-Sinai Medical Center, European Commission, Deutsche Forschungsgemeinschaft, ZonMw, Erasmus Universiteit Rotterdam, Erasmus Medisch Centrum, Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Hjartavernd, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: G118440752, Family Blood Pressure Program (GenNet Network), G1220223050, G1325221871, G1332411685, G136105103, G1462415530, G215333750, G2194386449, G250621538, G250924255, G25881238, G277826483, G2800149121, G2818913090, G297113894, G3004700323, G3236609591, G328935669, G36937976, G3839646794, G390162502, G4048755144, G423252844, G494123624, G5164707915, G528395701, G536099884, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, G5451084504, Epidemiology of Venous Thrombosis and Pulmonary Embolism, CHS Events Follow-up Study, G6203107232, G6226795708, General Clinical Research Center, G786153652, G793702358, G7999488110, G812579647, MOLECULAR EPIDEMIOLOGY OF ESSENTIAL HYPERTENSION, G8486527673, G8593276544, G9000113536, Framingham Project/Levy, From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, G905887895, G931818222, G939135972
OpenAlex ID: W2056367362