Title | Genome-wide association study of blood pressure and hypertension. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Levy, D, Ehret, GB, Rice, K, Verwoert, GC, Launer, LJ, Dehghan, A, Glazer, NL, Morrison, AC, Johnson, AD, Aspelund, T, Aulchenko, Y, Lumley, T, Köttgen, A, Vasan, RS, Rivadeneira, F, Eiriksdottir, G, Guo, X, Arking, DE, Mitchell, GF, Mattace-Raso, FUS, Smith, AV, Taylor, K, Scharpf, RB, Hwang, S-J, Sijbrands, EJG, Bis, J, Harris, TB, Ganesh, SK, O'Donnell, CJ, Hofman, A, Rotter, JI, Coresh, J, Benjamin, EJ, Uitterlinden, AG, Heiss, G, Fox, CS, Witteman, JCM, Boerwinkle, E, Wang, TJ, Gudnason, V, Larson, MG, Chakravarti, A, Psaty, BM, van Duijn, CM |
Journal | Nat Genet |
Volume | 41 |
Issue | 6 |
Pagination | 677-87 |
Date Published | 2009 Jun |
ISSN | 1546-1718 |
Keywords | Blood Pressure, Cell Line, Chromosome Mapping, Chromosomes, Human, Diastole, Gene Expression Regulation, Genetic Association Studies, Genome-Wide Association Study, Humans, Hypertension, Liver, Lymphocytes, Meta-Analysis as Topic, Odds Ratio, Phenotype, Prevalence, Risk Assessment, Systole |
Abstract | <p>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.</p> |
DOI | 10.1038/ng.384 |
Alternate Journal | Nat. Genet. |
PubMed ID | 19430479 |
PubMed Central ID | PMC2998712 |
Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01 HC055022 / HC / NHLBI NIH HHS / United States N01 HC085086 / HC / NHLBI NIH HHS / United States R01 HL059367-02 / HL / NHLBI NIH HHS / United States N01AG12100 / AG / NIA NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States U01 HG004402-01 / HG / NHGRI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01 HC075150 / HC / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States N01 HC055018 / HC / NHLBI NIH HHS / United States N01 HC025195 / HC / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States R37 HL051021-06 / HL / NHLBI NIH HHS / United States U01 HL080295-01 / HL / NHLBI NIH HHS / United States R01 HL087652-01 / HL / NHLBI NIH HHS / United States R37 HL051021-12 / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States HHSN268200625226C / / PHS HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States N02 HL64278 / HL / WHI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States R01 HL086694-01A1 / HL / NHLBI NIH HHS / United States R37 HL051021-13 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States P30 DK063491-039004 / DK / NIDDK NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States N01 HC055018 / HC / WHI NIH HHS / United States N01 HC055019 / HC / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States / / Intramural NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States U10 HL054512-05 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01 HC055222 / HC / NHLBI NIH HHS / United States N01 AG012100 / AG / WHI NIH HHS / United States R37HL051021 / HL / NHLBI NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States R37 HL051021-11 / HL / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States P30 DK063491-029004 / DK / NIDDK NIH HHS / United States N01 HC085079 / HC / WHI NIH HHS / United States N01 HC055015 / HC / NHLBI NIH HHS / United States N01 HC055021 / HC / NHLBI NIH HHS / United States N01 HC045133 / HC / WHI NIH HHS / United States UL1 RR025005-01 / RR / NCRR NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States P30 DK063491-019004 / DK / NIDDK NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States R01 HL087641-01 / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States N01 HC055020 / HC / NHLBI NIH HHS / United States P30 DK063491-049004 / DK / NIDDK NIH HHS / United States U10HL054512 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC085079 / HC / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States N01 HC055019 / HC / WHI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States R37 HL051021-14 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States R37 HL051021-15 / HL / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R37 HL051021 / HL / NHLBI NIH HHS / United States R37 HL051021-10 / HL / NHLBI NIH HHS / United States N01 HC055016 / HC / NHLBI NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States U10 HL054512 / HL / NHLBI NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States |