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Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction
- Source :
- Nature genetics; vol 42, iss 12, 1068-1076; 1061-4036
- Publication Year :
- 2010
-
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.
Details
- Database :
- OAIster
- Journal :
- Nature genetics; vol 42, iss 12, 1068-1076; 1061-4036
- Notes :
- application/pdf, Nature genetics vol 42, iss 12, 1068-1076 1061-4036
- Publication Type :
- Electronic Resource
- Accession number :
- edsoai.on1287368065
- Document Type :
- Electronic Resource