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

TitleCommon variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.
Publication TypeJournal Article
Year of Publication2010
AuthorsSotoodehnia, N, Isaacs A, de Bakker PIW, Dörr M, Newton-Cheh C, Nolte IM, van der Harst P, Müller M, Eijgelsheim M, Alonso A et al.
JournalNature genetics
Volume42
Issue12
Pagination1068-76
Date Published2010 Dec
ISSN1546-1718
KeywordsAnimals, Animals, Newborn, Chromosomes, Human, Computational Biology, Electrocardiography, Genetic Loci, Genome-Wide Association Study, Heart Conduction System, Humans, Mice, Mice, Transgenic, Models, Animal, Myocytes, Cardiac, Polymorphism, Single Nucleotide, Sodium Channels
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.

DOI10.1038/ng.2250
Alternate JournalNat. Genet.