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Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

TitleGenome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.
Publication TypeJournal Article
Year of Publication2011
AuthorsWain LV, Verwoert GC, O'Reilly PF, et al.
Secondary Authorsvan Duijn CM
Corporate AuthorsLifeLines Cohort Study, ECHOGen Consortium, AortaGen Consortium, CHARGE Consortium Heart Failure Working Group, KidneyGen consortium, CKDGen Consortium, Cardiogenics Consortium, CARDIOGRAM
JournalNat Genet
Volume43
Issue10
Pagination1005-11
Date Published2011 Sep 11
ISSN1546-1718
KeywordsArteries, Blood Pressure, Case-Control Studies, Follow-Up Studies, Genetic Loci, Genome-Wide Association Study, Humans, Hypertension, Linkage Disequilibrium, Polymorphism, Single Nucleotide
Abstract

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

DOI10.1038/ng.922
Alternate JournalNat Genet
PubMed ID21909110
PubMed Central IDPMC3445021
Grant ListG0801056 / MRC_ / Medical Research Council / United Kingdom
R01 HL043851 / HL / NHLBI NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
G1000143 / MRC_ / Medical Research Council / United Kingdom
MC_U106179471 / MRC_ / Medical Research Council / United Kingdom
MC_PC_U127592696 / MRC_ / Medical Research Council / United Kingdom
G0401527 / MRC_ / Medical Research Council / United Kingdom
N01 HC055015 / HC / NHLBI NIH HHS / United States
G0902313 / MRC_ / Medical Research Council / United Kingdom
G0700704 / MRC_ / Medical Research Council / United Kingdom
N01 HC085079 / HC / NHLBI NIH HHS / United States
MC_U106188470 / MRC_ / Medical Research Council / United Kingdom
K23 HL080025 / HL / NHLBI NIH HHS / United States
ETM/55 / CSO_ / Chief Scientist Office / United Kingdom
CZB/4/505 / CSO_ / Chief Scientist Office / United Kingdom
CZB/4/710 / CSO_ / Chief Scientist Office / United Kingdom
G9521010 / MRC_ / Medical Research Council / United Kingdom
MC_U127561128 / MRC_ / Medical Research Council / United Kingdom
G0700931 / MRC_ / Medical Research Council / United Kingdom
MC_U137686857 / MRC_ / Medical Research Council / United Kingdom
G0601966 / MRC_ / Medical Research Council / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States
263 MD9164 13 / MD / NIMHD NIH HHS / United States
Z01 HG000024-13 / ImNIH / Intramural NIH HHS / United States
G0701863 / MRC_ / Medical Research Council / United Kingdom
090532 / WT_ / Wellcome Trust / United Kingdom
N01 AG012109 / AG / NIA NIH HHS / United States
MC_PC_U127561128 / MRC_ / Medical Research Council / United Kingdom
BB/F019394/1 / BB_ / Biotechnology and Biological Sciences Research Council / United Kingdom
MC_U127592696 / MRC_ / Medical Research Council / United Kingdom
U10 HL054512 / HL / NHLBI NIH HHS / United States
N01 HC095159 / HC / NHLBI NIH HHS / United States