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Title: Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.
Authors: Sotoodehnia, N
Isaacs, A
de Bakker PI
Dörr, M
Newton-Cheh, C
Nolte, IM
van der Harst P
Müller, M
Eijgelsheim, M
Alonso, A
Hicks, AA
Padmanabhan, S
Hayward, C
Smith, AV
Polasek, O
Giovannone, S
Fu, J
Magnani, JW
Marciante, KD
Pfeufer, A
Gharib, SA
Teumer, A
Li, M
Bis, JC
Rivadeneira, F
Aspelund, T
Köttgen, A
Johnson, T
Rice, K
Sie, MP
Wang, YA
Klopp, N
Fuchsberger, C
Wild, SH
Mateo Leach I
Estrada, K
Völker, U
Wright, AF
Asselbergs, FW
Qu, J
Chakravarti, A
Sinner, MF
Kors, JA
Petersmann, A
Harris, TB
Soliman, EZ
Munroe, PB
Psaty, BM
Oostra, BA
Cupples, LA
Perz, S
de Boer RA
Uitterlinden, AG
Völzke, H
Spector, TD
Liu, FY
Boerwinkle, E
Dominiczak, AF
Rotter, JI
van Herpen G
Levy, D
Wichmann, HE
van Gilst WH
Witteman, JC
Kroemer, HK
Kao, WH
Heckbert, SR
Meitinger, T
Hofman, A
Campbell, H
Folsom, AR
van Veldhuisen DJ
Schwienbacher, C
O'Donnell, CJ
Volpato, CB
Caulfield, MJ
Connell, JM
Launer, L
Lu, X
Franke, L
Fehrmann, RS
te Meerman G
Groen, HJ
Weersma, RK
van den Berg LH
Wijmenga, C
Ophoff, RA
Navis, G
Rudan, I
Snieder, H
Wilson, JF
Pramstaller, PP
Siscovick, DS
Wang, TJ
Gudnason, V
van Duijn CM
Felix, SB
Fishman, GI
Jamshidi, Y
Stricker, BH
Samani, NJ
Kääb, S
Arking, DE
First Published: Dec-2010
Citation: NAT GENET, 2010, 42 (12), pp. 1068-1076
Abstract: 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.
DOI Link: 10.1038/ng.716
eISSN: 1546-1718
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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