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Nat Genet. 2009 Apr;41(4):407-14. doi: 10.1038/ng.362. Epub 2009 Mar 22.

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

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1
Institute of Human Genetics, Helmholtz Center Munich, Germany. arne.pfeufer@helmholtz-muenchen.de

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.

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PMID:
19305409
PMCID:
PMC2976045
DOI:
10.1038/ng.362
[Indexed for MEDLINE]
Free PMC Article

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