Authors
Nona Sotoodehnia, Aaron Isaacs, Paul IW 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, Sina A Gharib, Alexander Teumer, Man Li, Joshua C Bis, Fernando Rivadeneira, Thor Aspelund, Anna Köttgen, Toby Johnson, Kenneth Rice, Mark PS 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 CM Witteman, Heyo K Kroemer, WH 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 SN Fehrmann, Gerard Te Meerman, Harry JM 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
Publication date
2010/12
Journal
Nature genetics
Volume
42
Issue
12
Pages
1068-1076
Publisher
Nature Publishing Group US
Description
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 …
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