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Sotoodehnia, N; Isaacs, A; de Bakker, PI; Dörr, M; Newton-Cheh, C; Nolte, IM; van der Harst, P; Müller, M; Eijgelsheim, M; Alonso, A; Hicks, AA; Padmanabhan, S; Hayward, C; Smith, AV; Polasek, O; Giovannone, S; Fu, J; Magnani, JW; Marciante, KD; Pfeufer, A; Gharib, SA; Teumer, A; Li, M; Bis, JC; Rivadeneira, F; Aspelund, T; Köttgen, A; Johnson, T; Rice, K; Sie, MP; Wang, YA; Klopp, N; Fuchsberger, C; Wild, SH; Mateo Leach, I; Estrada, K; Völker, U; Wright, AF; Asselbergs, FW; Qu, J; Chakravarti,...    »
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. 
Nat Genet 
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r Humangenetik