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

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.

SUBMITTER: Nolte IM

PROVIDER: S-EPMC2704957 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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

Nolte Ilja M IM Wallace Chris C Newhouse Stephen J SJ Waggott Daryl D Fu Jingyuan J Soranzo Nicole N Gwilliam Rhian R Deloukas Panos P Savelieva Irina I Zheng Dongling D Dalageorgou Chrysoula C Farrall Martin M Samani Nilesh J NJ Connell John J Brown Morris M Dominiczak Anna A Lathrop Mark M Zeggini Eleftheria E Wain Louise V LV Newton-Cheh Christopher C Eijgelsheim Mark M Rice Kenneth K de Bakker Paul I W PI Pfeufer Arne A Sanna Serena S Arking Dan E DE Asselbergs Folkert W FW Spector Tim D TD Carter Nicholas D ND Jeffery Steve S Tobin Martin M Caulfield Mark M Snieder Harold H Paterson Andrew D AD Munroe Patricia B PB Jamshidi Yalda Y

PloS one 20090709 7

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 compari ...[more]

PMID: 19587794

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Dataset Information

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

Publications

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

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