Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction
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.
|Persistent URL||dx.doi.org/10.1038/ng.716, hdl.handle.net/1765/28354|
Sotoodehnia, N., Isaacs, A.J., de Bakker, P.I.W., Dörr, M., Newton-Cheh, C., Nolte, I.M., … Wang, T.J.. (2010). Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction. Nature Genetics, 42(12), 1068–1076. doi:10.1038/ng.716