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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; Jingyuan Fu; Soranzo, Nicole; Gwilliam, Rhian; Deloukas, Panos; Savelieva, Irina; Dongling Zheng; Dalageorgou, Chrysoula; Farrall, Martin; Samani, Nilesh J.; Connell, John; Brown, Morris; Dominiczak, Anna; Lathrop, Mark; Eleftheria Zeggini; Wain, Louise V.; Newton-Cheh, Christopher
- 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<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.
- Subjects
NORTH America; UNITED States; META-analysis; ARRHYTHMIA; HEART beat; CARDIAC arrest; HEART diseases; PALPITATION; LOCUS (Genetics)
- Publication
PLoS ONE, 2009, Vol 4, Issue 7, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0006138