Genome-wide association study of PR interval.
The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8). At the 3p22.2 locus, we observed two independent associations in voltage-gated sodium channel genes, SCN10A and SCN5A. Six of the loci were near cardiac developmental genes, including CAV1-CAV2, NKX2-5 (CSX1), SOX5, WNT11, MEIS1, and TBX5-TBX3, providing pathophysiologically interesting candidate genes. Five of the loci, SCN5A, SCN10A, NKX2-5, CAV1-CAV2, and SOX5, were also associated with atrial fibrillation (N = 5,741 cases, P < 0.0056). This suggests a role for common variation in ion channel and developmental genes in atrial and atrioventricular conduction as well as in susceptibility to atrial fibrillation.
Pfeufer
Arne
A
Institute of Human Genetics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany. arne.pfeufer@web.de
van Noord
Charlotte
C
Marciante
Kristin D
KD
Arking
Dan E
DE
Larson
Martin G
MG
Smith
Albert Vernon
AV
Tarasov
Kirill V
KV
Müller
Martina
M
Sotoodehnia
Nona
N
Sinner
Moritz F
MF
Verwoert
Germaine C
GC
Li
Man
M
Kao
W H Linda
WH
Köttgen
Anna
A
Coresh
Josef
J
Bis
Joshua C
JC
Psaty
Bruce M
BM
Rice
Kenneth
K
Rotter
Jerome I
JI
Rivadeneira
Fernando
F
Hofman
Albert
A
Kors
Jan A
JA
Stricker
Bruno H C
BH
Uitterlinden
André G
AG
van Duijn
Cornelia M
CM
Beckmann
Britt M
BM
Sauter
Wiebke
W
Gieger
Christian
C
Lubitz
Steven A
SA
Newton-Cheh
Christopher
C
Wang
Thomas J
TJ
Magnani
Jared W
JW
Schnabel
Renate B
RB
Chung
Mina K
MK
Barnard
John
J
Smith
Jonathan D
JD
Van Wagoner
David R
DR
Vasan
Ramachandran S
RS
Aspelund
Thor
T
Eiriksdottir
Gudny
G
Harris
Tamara B
TB
Launer
Lenore J
LJ
Najjar
Samer S
SS
Lakatta
Edward
E
Schlessinger
David
D
Uda
Manuela
M
Abecasis
Gonçalo R
GR
Müller-Myhsok
Bertram
B
Ehret
Georg B
GB
Boerwinkle
Eric
E
Chakravarti
Aravinda
A
Soliman
Elsayed Z
EZ
Lunetta
Kathryn L
KL
Perz
Siegfried
S
Wichmann
H-Erich
HE
Meitinger
Thomas
T
Levy
Daniel
D
Gudnason
Vilmundur
V
Ellinor
Patrick T
PT
Sanna
Serena
S
Kääb
Stefan
S
Witteman
Jacqueline C M
JC
Alonso
Alvaro
A
Benjamin
Emelia J
EJ
Heckbert
Susan R
SR
D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics / Q000503:physiopathology; D015331:Cohort Studies; D004562:Electrocardiography; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006329:Heart Conduction System / Q000502:physiology*; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic