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Nat Genet. 2010 Dec;42(12):1068-76. doi: 10.1038/ng.716. Epub 2010 Nov 14.

Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.

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1
Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington, USA. nsotoo@u.washington.edu

Abstract

The QRS interval, from the beginning of the Q wave to the end of the S wave on an electrocardiogram, reflects ventricular depolarization and conduction time and is a risk factor for mortality, sudden death and heart failure. We performed a genome-wide association meta-analysis in 40,407 individuals of European descent from 14 studies, with further genotyping in 7,170 additional Europeans, and we identified 22 loci associated with QRS duration (P < 5 × 10(-8)). These loci map in or near genes in pathways with established roles in ventricular conduction such as sodium channels, transcription factors and calcium-handling proteins, but also point to previously unidentified biologic processes, such as kinase inhibitors and genes related to tumorigenesis. We demonstrate that SCN10A, a candidate gene at the most significantly associated locus in this study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN10A blocker prolongs QRS duration. These findings extend our current knowledge of ventricular depolarization and conduction.

PMID:
21076409
PMCID:
PMC3338195
DOI:
10.1038/ng.716
[Indexed for MEDLINE]
Free PMC Article

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