- Main
Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.
- Author(s): Sotoodehnia, Nona;
- Isaacs, Aaron;
- de Bakker, Paul IW;
- Dörr, Marcus;
- Newton-Cheh, Christopher;
- Nolte, Ilja M;
- van der Harst, Pim;
- Müller, Martina;
- Eijgelsheim, Mark;
- Alonso, Alvaro;
- Hicks, Andrew A;
- Padmanabhan, Sandosh;
- Hayward, Caroline;
- Smith, Albert Vernon;
- Polasek, Ozren;
- Giovannone, Steven;
- Fu, Jingyuan;
- Magnani, Jared W;
- Marciante, Kristin D;
- Pfeufer, Arne;
- Gharib, Sina A;
- Teumer, Alexander;
- Li, Man;
- Bis, Joshua C;
- Rivadeneira, Fernando;
- Aspelund, Thor;
- Köttgen, Anna;
- Johnson, Toby;
- Rice, Kenneth;
- Sie, Mark PS;
- Wang, Ying A;
- Klopp, Norman;
- Fuchsberger, Christian;
- Wild, Sarah H;
- Mateo Leach, Irene;
- Estrada, Karol;
- Völker, Uwe;
- Wright, Alan F;
- Asselbergs, Folkert W;
- Qu, Jiaxiang;
- Chakravarti, Aravinda;
- Sinner, Moritz F;
- Kors, Jan A;
- Petersmann, Astrid;
- Harris, Tamara B;
- Soliman, Elsayed Z;
- Munroe, Patricia B;
- Psaty, Bruce M;
- Oostra, Ben A;
- Cupples, L Adrienne;
- Perz, Siegfried;
- de Boer, Rudolf A;
- Uitterlinden, André G;
- Völzke, Henry;
- Spector, Timothy D;
- Liu, Fang-Yu;
- Boerwinkle, Eric;
- Dominiczak, Anna F;
- Rotter, Jerome I;
- van Herpen, Gé;
- Levy, Daniel;
- Wichmann, H-Erich;
- van Gilst, Wiek H;
- Witteman, Jacqueline CM;
- Kroemer, Heyo K;
- Kao, WH Linda;
- Heckbert, Susan R;
- Meitinger, Thomas;
- Hofman, Albert;
- Campbell, Harry;
- Folsom, Aaron R;
- van Veldhuisen, Dirk J;
- Schwienbacher, Christine;
- O'Donnell, Christopher J;
- Volpato, Claudia Beu;
- Caulfield, Mark J;
- Connell, John M;
- Launer, Lenore;
- Lu, Xiaowen;
- Franke, Lude;
- Fehrmann, Rudolf SN;
- te Meerman, Gerard;
- Groen, Harry JM;
- Weersma, Rinse K;
- van den Berg, Leonard H;
- Wijmenga, Cisca;
- Ophoff, Roel A;
- Navis, Gerjan;
- Rudan, Igor;
- Snieder, Harold;
- Wilson, James F;
- Pramstaller, Peter P;
- Siscovick, David S;
- Wang, Thomas J;
- Gudnason, Vilmundur;
- van Duijn, Cornelia M;
- Felix, Stephan B;
- Fishman, Glenn I;
- Jamshidi, Yalda;
- Stricker, Bruno H Ch;
- Samani, Nilesh J;
- Kääb, Stefan;
- Arking, Dan E
- et al.
Published Web Location
https://doi.org/10.1038/ng.716Abstract
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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