Common variants in KCNN3 are associated with lone atrial fibrillation.
Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF. This condition affects a subset of individuals without overt heart disease and with an increased heritability of AF. We report a meta-analysis of genome-wide association studies conducted using 1,335 individuals with lone AF (cases) and 12,844 unaffected individuals (referents). Cases were obtained from the German AF Network, Heart and Vascular Health Study, the Atherosclerosis Risk in Communities Study, the Cleveland Clinic and Massachusetts General Hospital. We identified an association on chromosome 1q21 to lone AF (rs13376333, adjusted odds ratio = 1.56; P = 6.3 x 10(-12)), and we replicated this association in two independent cohorts with lone AF (overall combined odds ratio = 1.52, 95% CI 1.40-1.64; P = 1.83 x 10(-21)). rs13376333 is intronic to KCNN3, which encodes a potassium channel protein involved in atrial repolarization.
Ellinor
Patrick T
PT
[1] Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts, USA. [3] Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA. [4] These authors contributed equally to this work.
Lunetta
Kathryn L
KL
Glazer
Nicole L
NL
Pfeufer
Arne
A
Alonso
Alvaro
A
Chung
Mina K
MK
Sinner
Moritz F
MF
de Bakker
Paul I W
PI
Mueller
Martina
M
Lubitz
Steven A
SA
Fox
Ervin
E
Darbar
Dawood
D
Smith
Nicholas L
NL
Smith
Jonathan D
JD
Schnabel
Renate B
RB
Soliman
Elsayed Z
EZ
Rice
Kenneth M
KM
Van Wagoner
David R
DR
Beckmann
Britt-M
BM
van Noord
Charlotte
C
Wang
Ke
K
Ehret
Georg B
GB
Rotter
Jerome I
JI
Hazen
Stanley L
SL
Steinbeck
Gerhard
G
Smith
Albert V
AV
Launer
Lenore J
LJ
Harris
Tamara B
TB
Makino
Seiko
S
Nelis
Mari
M
Milan
David J
DJ
Perz
Siegfried
S
Esko
Tõnu
T
Köttgen
Anna
A
Moebus
Susanne
S
Newton-Cheh
Christopher
C
Li
Man
M
Möhlenkamp
Stefan
S
Wang
Thomas J
TJ
Kao
W H Linda
WH
Vasan
Ramachandran S
RS
Nöthen
Markus M
MM
MacRae
Calum A
CA
Stricker
Bruno H Ch
BH
Hofman
Albert
A
Uitterlinden
André G
AG
Levy
Daniel
D
Boerwinkle
Eric
E
Metspalu
Andres
A
Topol
Eric J
EJ
Chakravarti
Aravinda
A
Gudnason
Vilmundur
V
Psaty
Bruce M
BM
Roden
Dan M
DM
Meitinger
Thomas
T
Wichmann
H-Erich
HE
Witteman
Jacqueline C M
JC
Barnard
John
J
Arking
Dan E
DE
Benjamin
Emelia J
EJ
Heckbert
Susan R
SR
Kääb
Stefan
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D001281:Atrial Fibrillation / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics*; D055815:Young Adult
C406328:KCNN3 protein, human; D051640:Small-Conductance Calcium-Activated Potassium Channels