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Sotoodehnia, N.* ; Isaacs, A.* ; de Bakker, P.I.W.* ; Dörr, M.* ; Newton-Cheh, C.* ; Nolte, I.M.* ; van der Harst, P.* ; Müller, M. ; Eijgelsheim, M.* ; Alonso, A.* ; Hicks, A.A.* ; Padmanabhan, S.* ; Hayward, C.* ; Smith, A.V.* ; Polasek, O.* ; Giovannone, S.* ; Fu, J.Y.* ; Magnani, J.W.* ; Marciante, K.D.* ; Pfeufer, A. ; Gharib, S.A.* ; Teumer, A.* ; Li, M.* ; Bis, J.C.* ; Rivadeneira, F.* ; Aspelund, T.* ; Köttgen, A.* ; Johnson, T.* ; Rice, K.* ; Sie, M.P.S.* ; Wang, Y.A.* ; Klopp, N. ; Fuchsberger, C.* ; Wild, S.H.* ; Leach, I.M.* ; Estrada, K.* ; Völker, U.* ; Wright, A.F.* ; Asselbergs, F.W.* ; Qu, J.X.* ; Chakravarti, A.* ; Sinner, M.F.* ; Kors, J.A.* ; Petersmann, A.* ; Harris, T.B.* ; Soliman, E.Z.* ; Munroe, P.B.* ; Psaty, B.M.* ; Oostra, B.A.* ; Cupples, L.A.* ; Perz, S. ; de Boer, R.A.* ; Uitterlinden, A.G.* ; Völzke, H.* ; Spector, T.D.* ; Liu, F.Y.* ; Boerwinkle, E.* ; Dominiczak, A.F.* ; Rotter, J.I.* ; van Herpen, G.* ; Levy, D.* ; Wichmann, H.-E. ; van Gilst, W.H.* ; Witteman, J.C.M.* ; Kroemer, H.K.* ; Kao, W.H.L.* ; Heckbert, S.R.* ; Meitinger, T. ; Hofman, A.* ; Campbell, H.* ; Folsom, A.R.* ; van Veldhuisen, D.J.* ; Schwienbacher, C.* ; O'Donnell, C.J.* ; Volpato, C.B.* ; Caulfield, M.J.* ; Connell, J.M.* ; Launer, L.* ; Lu, X.W.* ; Franke, L.* ; Fehrmann, R.S.N.* ; Meerman, G.T.* ; Groen, H.J.M.* ; Weersma, R.K.* ; van den Berg, L.H.* ; Wijmenga, C.* ; Ophoff, R.A.* ; Navis, G.* ; Rudan, I.* ; Snieder, H.* ; Wilson, J.F.* ; Pramstaller, P.P.* ; Siscovick, D.S.* ; Wang, T.J.* ; Gudnason, V.* ; van Duijn, C.M.* ; Felix, S.B.* ; Fishman, G.I.* ; Jamshidi, Y.* ; Stricker, B.H.C.* ; Samani, N.J.* ; Kääb, S.* ; Arking, D.E.*

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

Nat. Genet. 42, 1068-1076 (2010)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Genome-wide association; QT interval duration; Rich repeat protein; Heart-rate; Transcription factor; Gene-expression; PR interval; System; Disease; Electrocardiogram
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 42, Issue: 12, Pages: 1068-1076 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
Institute of Biological and Medical Imaging (IBMI)