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

Authors:
Sina A Gharib, MD
Sina A Gharib, MD
Center for Lung Biology, UW Medicine Sleep Center, University of Washington
Associate Professor
Seattle, WA | United States
Nona Sotoodehnia Aaron Isaacs Paul I W de Bakker Marcus Dörr Christopher Newton-Cheh Ilja M Nolte Pim van der Harst Martina Müller Mark Eijgelsheim Alvaro Alonso Andrew A Hicks Sandosh Padmanabhan Caroline Hayward Albert Vernon Smith Ozren Polasek Steven Giovannone Jingyuan Fu Jared W Magnani Kristin D Marciante Arne Pfeufer Alexander Teumer Man Li Joshua C Bis Fernando Rivadeneira Thor Aspelund Anna Köttgen Toby Johnson Kenneth Rice Mark P S Sie Ying A Wang Norman Klopp Christian Fuchsberger Sarah H Wild Irene Mateo Leach Karol Estrada Uwe Völker Alan F Wright Folkert W Asselbergs Jiaxiang Qu Aravinda Chakravarti Moritz F Sinner Jan A Kors Astrid Petersmann Tamara B Harris Elsayed Z Soliman Patricia B Munroe Bruce M Psaty Ben A Oostra L Adrienne Cupples Siegfried Perz Rudolf A de Boer André G Uitterlinden Henry Völzke Timothy D Spector Fang-Yu Liu Eric Boerwinkle Anna F Dominiczak Jerome I Rotter Gé van Herpen Daniel Levy H-Erich Wichmann Wiek H van Gilst Jacqueline C M Witteman Heyo K Kroemer W H Linda Kao Susan R Heckbert Thomas Meitinger Albert Hofman Harry Campbell Aaron R Folsom Dirk J van Veldhuisen Christine Schwienbacher Christopher J O'Donnell Claudia Beu Volpato Mark J Caulfield John M Connell Lenore Launer Xiaowen Lu Lude Franke Rudolf S N Fehrmann Gerard te Meerman Harry J M Groen Rinse K Weersma Leonard H van den Berg Cisca Wijmenga Roel A Ophoff Gerjan Navis Igor Rudan Harold Snieder James F Wilson Peter P Pramstaller David S Siscovick Thomas J Wang Vilmundur Gudnason Cornelia M van Duijn Stephan B Felix Glenn I Fishman Yalda Jamshidi Bruno H Ch Stricker Nilesh J Samani Stefan Kääb Dan E Arking

Nat Genet 2010 Dec 14;42(12):1068-76. Epub 2010 Nov 14.

Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington, USA.

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.

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http://dx.doi.org/10.1038/ng.716DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338195PMC
December 2010
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