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Effects of rare and common blood pressure gene variants on essential hypertension: results from the Family Blood Pressure Program, CLUE, and Atherosclerosis Risk in Communities studies.

TitleEffects of rare and common blood pressure gene variants on essential hypertension: results from the Family Blood Pressure Program, CLUE, and Atherosclerosis Risk in Communities studies.
Publication TypeJournal Article
Year of Publication2013
AuthorsNguyen K-DH, Pihur V, Ganesh SK, Rakha A, Cooper RS, Hunt SC, Freedman BI, Coresh JJ, Kao LWH, Morrison AC, Boerwinkle E, Ehret GB
Secondary AuthorsChakravarti A
JournalCirc Res
Volume112
Issue2
Pagination318-26
Date Published2013 Jan 18
ISSN1524-4571
KeywordsAfrican Americans, Asian Americans, Atherosclerosis, Blood Pressure, Cohort Studies, European Continental Ancestry Group, Female, Genetic Association Studies, Genetic Variation, Hispanic Americans, Humans, Hypertension, Male, Middle Aged, National Heart, Lung, and Blood Institute (U.S.), Population Surveillance, Prospective Studies, Residence Characteristics, United States
Abstract

RATIONALE: Hypertension affects ≈30% of adults in industrialized countries and is the major risk factor for cardiovascular disease.

OBJECTIVE: We sought to study the genetic effect of coding and conserved noncoding variants in syndromic hypertension genes on systolic blood pressure (BP) and diastolic BP to assess their overall impact on essential hypertension.

METHODS AND RESULTS: We resequenced 11 genes (AGT, CYP11B1, CYP17A1, HSD11B2, NR3C1, NR3C2, SCNN1A, SCNN1B, SCNN1G, WNK1, and WNK4) in 560 European American (EA) and African American ancestry GenNet participants with extreme systolic BP. We investigated genetic associations of 2535 variants with BP in 19997 EAs and in 6069 African Americans in 3 types of analyses. First, we studied the combined effects of all variants in GenNet. Second, we studied 1000 Genomes imputed polymorphic variants in 9747 EA and 3207 African American Atherosclerosis Risk in Communities subjects. Finally, we genotyped 37 missense and common noncoding variants in 6591 EAs and in 6521 individuals (3659 EA/2862 African American) from the CLUE and Family Blood Pressure Program studies, respectively. None of the variants individually reached significant false-discovery rates ≤0.05 for systolic BP and diastolic BP. However, on pooling all coding and noncoding variants, we identified at least 5 loci (AGT, CYP11B1, NR3C2, SCNN1G, and WNK1) with higher association at evolutionary conserved sites.

CONCLUSIONS: Both rare and common variants at these genes affect BP in the general population with modest effects sizes (

DOI10.1161/CIRCRESAHA.112.276725
Alternate JournalCirc Res
PubMed ID23149595
PubMed Central IDPMC3548950
Grant ListHHSN268201100012C / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
T32 GM007814 / GM / NIGMS NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100005C / / PHS HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
N01-HV-48194 / HV / NHLBI NIH HHS / United States
HHSN268201100009C / / PHS HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201100010C / / PHS HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / / PHS HHS / United States
HHSN268201100012C / / PHS HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
N01-HV-48196 / HV / NHLBI NIH HHS / United States
HHSN268201100007C / / PHS HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / / PHS HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
HL086694 / HL / NHLBI NIH HHS / United States
N01HV48196 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / / PHS HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
N01HV48194 / HL / NHLBI NIH HHS / United States