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.
National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA. levyd@nhlbi.nih.gov
Daniel
D
Levy
Georg B
GB
Ehret
Kenneth
K
Rice
Germaine C
GC
Verwoert
Lenore J
LJ
Launer
Abbas
A
Dehghan
Nicole L
NL
Glazer
Alanna C
AC
Morrison
Andrew D
AD
Johnson
Thor
T
Aspelund
Yurii
Y
Aulchenko
Thomas
T
Lumley
Anna
A
Köttgen
Ramachandran S
RS
Vasan
Fernando
F
Rivadeneira
Gudny
G
Eiriksdottir
Xiuqing
X
Guo
Dan E
DE
Arking
Gary F
GF
Mitchell
Francesco U S
FU
Mattace-Raso
Albert V
AV
Smith
Kent
K
Taylor
Robert B
RB
Scharpf
Shih-Jen
SJ
Hwang
Eric J G
EJ
Sijbrands
Joshua
J
Bis
Tamara B
TB
Harris
Santhi K
SK
Ganesh
Christopher J
CJ
O'Donnell
Albert
A
Hofman
Jerome I
JI
Rotter
Josef
J
Coresh
Emelia J
EJ
Benjamin
André G
AG
Uitterlinden
Gerardo
G
Heiss
Caroline S
CS
Fox
Jacqueline C M
JC
Witteman
Eric
E
Boerwinkle
Thomas J
TJ
Wang
Vilmundur
V
Gudnason
Martin G
MG
Larson
Aravinda
A
Chakravarti
Bruce M
BM
Psaty
Cornelia M
CM
van Duijn
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