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Common variants at ten loci modulate the QT interval duration in the QTSCD Study.

Authors :
Pfeufer A
Sanna S
Arking DE
Müller M
Gateva V
Fuchsberger C
Ehret GB
Orrú M
Pattaro C
Köttgen A
Perz S
Usala G
Barbalic M
Li M
Pütz B
Scuteri A
Prineas RJ
Sinner MF
Gieger C
Najjar SS
Kao WH
Mühleisen TW
Dei M
Happle C
Möhlenkamp S
Crisponi L
Erbel R
Jöckel KH
Naitza S
Steinbeck G
Marroni F
Hicks AA
Lakatta E
Müller-Myhsok B
Pramstaller PP
Wichmann HE
Schlessinger D
Boerwinkle E
Meitinger T
Uda M
Coresh J
Kääb S
Abecasis GR
Chakravarti A
Source :
Nature genetics [Nat Genet] 2009 Apr; Vol. 41 (4), pp. 407-14. Date of Electronic Publication: 2009 Mar 22.
Publication Year :
2009

Abstract

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.

Details

Language :
English
ISSN :
1546-1718
Volume :
41
Issue :
4
Database :
MEDLINE
Journal :
Nature genetics
Publication Type :
Academic Journal
Accession number :
19305409
Full Text :
https://doi.org/10.1038/ng.362