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

Autori
Sotoodehnia, Nona ; ... ; Polašek, Ozren ; Rudan, Igor ; ... ; Arking, D.E.

Izvornik
Nature genetics (1061-4036) 42 (2010), 12; 1068-1076

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
genome-wide; QRS

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti, Javno zdravstvo i zdravstvena zaštita

Napomena
The CHARGE Consortium (102 koautora)

POVEZANOST RADA