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Title: Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation: Meta-Analysis of Three Genome-Wide Association Studies
Authors: Nolte, Ilja M.
Wallace, Chris
Newhouse, Stephen J.
Waggott, Daryl
Fu, Jingyuan
Soranzo, Nicole
Gwilliam, Rhian
Deloukas, Panos
Savelieva, Irina
Zheng, Dongling
Dalageorgou, Chrysoula
Farrall, Martin
Samani, Nilesh J.
Connell, John M.
Brown, Morris
Dominiczak, Anna
Lathrop, Mark
Zeggini, Eleftheria
Wain, Louise V.
Newton-Cheh, Christopher
Eijgelsheim, Mark
Rice, Kenneth
de Bakker, Paul I.W.
Pfeufer, Arne
Sanna, Serena
Arking, Dan E.
Asselbergs, Folkert W.
Spector, Tim D.
Carter, Nicholas D.
Jeffery, Steve
Tobin, Martin D.
Caulfield, Mark J.
Snieder, Harold
Paterson, Andrew D.
Munroe, Patricia B.
Jamshidi, Yalda
First Published: Jul-2009
Publisher: Public Library of Science, PLoS
Citation: PLoS One, 2009, 4 (7), e6138
Abstract: 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<1×10−6. 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 = 1.4×10−83) and the phospholamban (PLN) gene (P = 1.9×10−29). 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.
DOI Link: 10.1371/journal.pone.0006138
eISSN: 1932-6203
Version: Publisher Version
Status: Peer-reviewed
Type: Article
Rights: Copyright © 2009 Nolte et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Health Sciences

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