PuSH - Publication Server of Helmholtz Zentrum München: Common genetic variation near the <em>Phospholamban </em>gene is associated with cardiac repolarisation: Meta-analysis of three genome-wide association studies.

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Nolte, I.M.* ; Wallace,C.* ; Newhouse, S.J.* ; Waggott, D.* ; Fu, J.* ; Soranzo, N.* ; Gwilliam, R.* ; Deloukas, P.* ; Savelieva, I.* ; Zheng, D.* ; Dalageorgou, C.* ; Farrall, M.* ; Samani, N.J.* ; Connell, J.* ; Brown, M.* ; Dominiczak, A.* ; Lathrop, M* ; Zeggini, E.* ; Wain, L.V.* ; Newton-Cheh, C.* ; Eijgelsheim, M.* ; Rice, K.* ; de Bakker, P.I.* ; Pfeufer, A.* ; Sanna, S.* ; Arking, D.E.* ; Asselbergs, F.W.* ; Spector, T.D.* ; Carter, N.D.* ; Jeffery, S.* ; Tobin, M.* ; Caulfield, M.* ; Snieder, H.* ; Paterson, A.D.* ; Munroe, P.B.* ; Jamshidi, Y.*

Common genetic variation near the Phospholamban gene is associated with cardiac repolarisation: Meta-analysis of three genome-wide association studies.

PLoS ONE 4:e6138 (2009)

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To identify loci affecting the electrocardiographic QT interval, a measure of cardiac repolarisation associated with risk of ventricular arrhythmias and sudden cardiac death, we conducted a meta-analysis of three genome-wide association studies (GWAS) including 3,558 subjects from the TwinsUK and BRIGHT cohorts in the UK and the DCCT/EDIC cohort from North America. Five loci were significantly associated with QT interval at P<1x10(-6). To validate these findings we performed an in silico comparison with data from two QT consortia: QTSCD (n = 15,842) and QTGEN (n = 13,685). Analysis confirmed the association between common variants near NOS1AP (P = 1.4x10(-83)) and the phospholamban (PLN) gene (P = 1.9x10(-29)). The most associated SNP near NOS1AP (rs12143842) explains 0.82% variance; the SNP near PLN (rs11153730) explains 0.74% variance of QT interval duration. We found no evidence for interaction between these two SNPs (P = 0.99). PLN is a key regulator of cardiac diastolic function and is involved in regulating intracellular calcium cycling, it has only recently been identified as a susceptibility locus for QT interval. These data offer further mechanistic insights into genetic influence on the QT interval which may predispose to life threatening arrhythmias and sudden cardiac death.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

ISSN (print) / ISBN 1932-6203

Journal PLoS ONE

Quellenangaben Volume: 4, Issue: 7, Article Number: e6138

Publisher Public Library of Science (PLoS)

Publishing Place Lawrence, Kan.

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Human Genetics (IHG)