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- Title
Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.
- Authors
Sotoodehnia, Nona; Isaacs, Aaron; de Bakker, Paul I. W.; Dörr, Marcus; Newton-Cheh, Christopher; Nolte, Ilja M.; Van der Harst, Pim; Müller, Martina; Eijgelsheim, Mark; Alonso, Alvaro; Hicks, Andrew A.; Padmanabhan, Sandosh; Hayward, Caroline; Smith, Albert Vernon; Polasek, Ozren; Giovannone, Steven; Jingyuan Fu; Magnani, Jared W.; Marciante, Kristin D.; Pfeufer, Arne
- 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.
- Subjects
LOCUS (Genetics); HEART ventricles; ELECTROCARDIOGRAPHY; MORTALITY; HEART failure risk factors; PHYSIOLOGY
- Publication
Nature Genetics, 2010, Vol 42, Issue 12, p1068
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.716