Genome-wide association study identifies eight loci associated with blood pressure.
Elevated blood pressure is a common, heritable cause of cardiovascular disease worldwide. To date, identification of common genetic variants influencing blood pressure has proven challenging. We tested 2.5 million genotyped and imputed SNPs for association with systolic and diastolic blood pressure in 34,433 subjects of European ancestry from the Global BPgen consortium and followed up findings with direct genotyping (N ≤ 71,225 European ancestry, N ≤ 12,889 Indian Asian ancestry) and in silico comparison (CHARGE consortium, N = 29,136). We identified association between systolic or diastolic blood pressure and common variants in eight regions near the CYP17A1 (P = 7 × 10(-24)), CYP1A2 (P = 1 × 10(-23)), FGF5 (P = 1 × 10(-21)), SH2B3 (P = 3 × 10(-18)), MTHFR (P = 2 × 10(-13)), c10orf107 (P = 1 × 10(-9)), ZNF652 (P = 5 × 10(-9)) and PLCD3 (P = 1 × 10(-8)) genes. All variants associated with continuous blood pressure were associated with dichotomous hypertension. These associations between common variants and blood pressure and hypertension offer mechanistic insights into the regulation of blood pressure and may point to novel targets for interventions to prevent cardiovascular disease.
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. cnewtoncheh@chgr.mgh.harvard.edu
Christopher
C
Newton-Cheh
Toby
T
Johnson
Vesela
V
Gateva
Martin D
MD
Tobin
Murielle
M
Bochud
Lachlan
L
Coin
Samer S
SS
Najjar
Jing Hua
JH
Zhao
Simon C
SC
Heath
Susana
S
Eyheramendy
Konstantinos
K
Papadakis
Benjamin F
BF
Voight
Laura J
LJ
Scott
Feng
F
Zhang
Martin
M
Farrall
Toshiko
T
Tanaka
Chris
C
Wallace
John C
JC
Chambers
Kay-Tee
KT
Khaw
Peter
P
Nilsson
Pim
P
van der Harst
Silvia
S
Polidoro
Diederick E
DE
Grobbee
N Charlotte
NC
Onland-Moret
Michiel L
ML
Bots
Louise V
LV
Wain
Katherine S
KS
Elliott
Alexander
A
Teumer
Jian'an
J
Luan
Gavin
G
Lucas
Johanna
J
Kuusisto
Paul R
PR
Burton
David
D
Hadley
Wendy L
WL
McArdle
Morris
M
Brown
Anna
A
Dominiczak
Stephen J
SJ
Newhouse
Nilesh J
NJ
Samani
John
J
Webster
Eleftheria
E
Zeggini
Jacques S
JS
Beckmann
Sven
S
Bergmann
Noha
N
Lim
Kijoung
K
Song
Peter
P
Vollenweider
Gerard
G
Waeber
Dawn M
DM
Waterworth
Xin
X
Yuan
Leif
L
Groop
Marju
M
Orho-Melander
Alessandra
A
Allione
Alessandra
A
Di Gregorio
Simonetta
S
Guarrera
Salvatore
S
Panico
Fulvio
F
Ricceri
Valeria
V
Romanazzi
Carlotta
C
Sacerdote
Paolo
P
Vineis
Inês
I
Barroso
Manjinder S
MS
Sandhu
Robert N
RN
Luben
Gabriel J
GJ
Crawford
Pekka
P
Jousilahti
Markus
M
Perola
Michael
M
Boehnke
Lori L
LL
Bonnycastle
Francis S
FS
Collins
Anne U
AU
Jackson
Karen L
KL
Mohlke
Heather M
HM
Stringham
Timo T
TT
Valle
Cristen J
CJ
Willer
Richard N
RN
Bergman
Mario A
MA
Morken
Angela
A
Döring
Christian
C
Gieger
Thomas
T
Illig
Thomas
T
Meitinger
Elin
E
Org
Arne
A
Pfeufer
H Erich
HE
Wichmann
Sekar
S
Kathiresan
Jaume
J
Marrugat
Christopher J
CJ
O'Donnell
Stephen M
SM
Schwartz
David S
DS
Siscovick
Isaac
I
Subirana
Nelson B
NB
Freimer
Anna-Liisa
AL
Hartikainen
Mark I
MI
McCarthy
Paul F
PF
O'Reilly
Leena
L
Peltonen
Anneli
A
Pouta
Paul E
PE
de Jong
Harold
H
Snieder
Wiek H
WH
van Gilst
Robert
R
Clarke
Anuj
A
Goel
Anders
A
Hamsten
John F
JF
Peden
Udo
U
Seedorf
Ann-Christine
AC
Syvänen
Giovanni
G
Tognoni
Edward G
EG
Lakatta
Serena
S
Sanna
Paul
P
Scheet
David
D
Schlessinger
Angelo
A
Scuteri
Marcus
M
Dörr
Florian
F
Ernst
Stephan B
SB
Felix
Georg
G
Homuth
Roberto
R
Lorbeer
Thorsten
T
Reffelmann
Rainer
R
Rettig
Uwe
U
Völker
Pilar
P
Galan
Ivo G
IG
Gut
Serge
S
Hercberg
G Mark
GM
Lathrop
Diana
D
Zelenika
Panos
P
Deloukas
Nicole
N
Soranzo
Frances M
FM
Williams
Guangju
G
Zhai
Veikko
V
Salomaa
Markku
M
Laakso
Roberto
R
Elosua
Nita G
NG
Forouhi
Henry
H
Völzke
Cuno S
CS
Uiterwaal
Yvonne T
YT
van der Schouw
Mattijs E
ME
Numans
Giuseppe
G
Matullo
Gerjan
G
Navis
Göran
G
Berglund
Sheila A
SA
Bingham
Jaspal S
JS
Kooner
John M
JM
Connell
Stefania
S
Bandinelli
Luigi
L
Ferrucci
Hugh
H
Watkins
Tim D
TD
Spector
Jaakko
J
Tuomilehto
David
D
Altshuler
David P
DP
Strachan
Maris
M
Laan
Pierre
P
Meneton
Nicholas J
NJ
Wareham
Manuela
M
Uda
Marjo-Riitta
MR
Jarvelin
Vincent
V
Mooser
Olle
O
Melander
Ruth J F
RJ
Loos
Paul
P
Elliott
Gonçalo R
GR
Abecasis
Mark
M
Caulfield
Patricia B
PB
Munroe
D048868:Adaptor Proteins, Signal Transducing; D001794:Blood Pressure / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000503:physiopathology; D002874:Chromosome Mapping; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D003971:Diastole / Q000235:genetics; D005060:Europe; D051521:Fibroblast Growth Factor 5 / Q000235:genetics; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D007194:India; D047908:Intracellular Signaling Peptides and Proteins; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D016366:Open Reading Frames / Q000235:genetics; D054803:Phospholipase C delta / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013599:Systole / Q000235:genetics; D044465:White People / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C496449:FGF5 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C490778:SH2B3 protein, human; C525993:ZNF652 protein, human; D051521:Fibroblast Growth Factor 5; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C518028:PLCD3 protein, human; D054803:Phospholipase C delta