- 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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