Common variants at ten loci modulate the QT interval duration in the QTSCD Study.
The QT interval, a measure of cardiac repolarization, predisposes to ventricular arrhythmias and sudden cardiac death (SCD) when prolonged or shortened. A common variant in NOS1AP is known to influence repolarization. We analyze genome-wide data from five population-based cohorts (ARIC, KORA, SardiNIA, GenNOVA and HNR) with a total of 15,842 individuals of European ancestry, to confirm the NOS1AP association and identify nine additional loci at P < 5 x 10(-8). Four loci map near the monogenic long-QT syndrome genes KCNQ1, KCNH2, SCN5A and KCNJ2. Two other loci include ATP1B1 and PLN, genes with established electrophysiological function, whereas three map to RNF207, near LITAF and within NDRG4-GINS3-SETD6-CNOT1, respectively, all of which have not previously been implicated in cardiac electrophysiology. These results, together with an accompanying paper from the QTGEN consortium, identify new candidate genes for ventricular arrhythmias and SCD.
Pfeufer
Arne
A
Institute of Human Genetics, Helmholtz Center Munich, Germany. arne.pfeufer@helmholtz-muenchen.de
Sanna
Serena
S
Arking
Dan E
DE
Müller
Martina
M
Gateva
Vesela
V
Fuchsberger
Christian
C
Ehret
Georg B
GB
Orrú
Marco
M
Pattaro
Cristian
C
Köttgen
Anna
A
Perz
Siegfried
S
Usala
Gianluca
G
Barbalic
Maja
M
Li
Man
M
Pütz
Benno
B
Scuteri
Angelo
A
Prineas
Ronald J
RJ
Sinner
Moritz F
MF
Gieger
Christian
C
Najjar
Samer S
SS
Kao
W H Linda
WH
Mühleisen
Thomas W
TW
Dei
Mariano
M
Happle
Christine
C
Möhlenkamp
Stefan
S
Crisponi
Laura
L
Erbel
Raimund
R
Jöckel
Karl-Heinz
KH
Naitza
Silvia
S
Steinbeck
Gerhard
G
Marroni
Fabio
F
Hicks
Andrew A
AA
Lakatta
Edward
E
Müller-Myhsok
Bertram
B
Pramstaller
Peter P
PP
Wichmann
H-Erich
HE
Schlessinger
David
D
Boerwinkle
Eric
E
Meitinger
Thomas
T
Uda
Manuela
M
Coresh
Josef
J
Kääb
Stefan
S
Abecasis
Gonçalo R
GR
Chakravarti
Aravinda
A
D001145:Arrhythmias, Cardiac / Q000235:genetics*; D002874:Chromosome Mapping; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D004594:Electrophysiology / Q000379:methods; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D014644:Genetic Variation; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D015203:Reproducibility of Results; D015222:Sodium Channels / Q000235:genetics
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D007473:Ion Channels; C000606913:KCNH2 protein, human; C489457:KCNJ2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024661:Potassium Channels, Inwardly Rectifying; C568320:SCN5A protein, human; D015222:Sodium Channels