Genome-wide association study of blood pressure and hypertension.
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.
Levy
Daniel
D
National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA. levyd@nhlbi.nih.gov
Ehret
Georg B
GB
Rice
Kenneth
K
Verwoert
Germaine C
GC
Launer
Lenore J
LJ
Dehghan
Abbas
A
Glazer
Nicole L
NL
Morrison
Alanna C
AC
Johnson
Andrew D
AD
Aspelund
Thor
T
Aulchenko
Yurii
Y
Lumley
Thomas
T
Köttgen
Anna
A
Vasan
Ramachandran S
RS
Rivadeneira
Fernando
F
Eiriksdottir
Gudny
G
Guo
Xiuqing
X
Arking
Dan E
DE
Mitchell
Gary F
GF
Mattace-Raso
Francesco U S
FU
Smith
Albert V
AV
Taylor
Kent
K
Scharpf
Robert B
RB
Hwang
Shih-Jen
SJ
Sijbrands
Eric J G
EJ
Bis
Joshua
J
Harris
Tamara B
TB
Ganesh
Santhi K
SK
O'Donnell
Christopher J
CJ
Hofman
Albert
A
Rotter
Jerome I
JI
Coresh
Josef
J
Benjamin
Emelia J
EJ
Uitterlinden
André G
AG
Heiss
Gerardo
G
Fox
Caroline S
CS
Witteman
Jacqueline C M
JC
Boerwinkle
Eric
E
Wang
Thomas J
TJ
Gudnason
Vilmundur
V
Larson
Martin G
MG
Chakravarti
Aravinda
A
Psaty
Bruce M
BM
van Duijn
Cornelia M
CM
D001794:Blood Pressure / Q000235:genetics*; D002460:Cell Line; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D003971:Diastole / Q000235:genetics; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000453:epidemiology / Q000235:genetics*; D008099:Liver / Q000502:physiology / Q000503:physiopathology; D008214:Lymphocytes / Q000502:physiology; D015201:Meta-Analysis as Topic; D016017:Odds Ratio; D010641:Phenotype; D015995:Prevalence; D018570:Risk Assessment; D013599:Systole / Q000235:genetics