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

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

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 BR...

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التفاصيل البيبلوغرافية
المؤلفون الرئيسيون: Nolte, I, Wallace, C, Newhouse, S, Waggott, D, Fu, J, Soranzo, N, Gwilliam, R, Deloukas, P, Savelieva, I, Zheng, D, Dalageorgou, C, Farrall, M, Samani, N, Connell, J, Brown, M, Dominiczak, A, Lathrop, M, Zeggini, E, Wain, L, Newton-Cheh, C, Eijgelsheim, M, Rice, K, de Bakker, P, Pfeufer, A, Sanna, S, Arking, D, Asselbergs, F, Spector, T, Carter, N, Jeffery, S, Tobin, M, Caulfield, M, Snieder, H, Paterson, A, Munroe, P, Jamshidi, Y
التنسيق: Journal article
اللغة:English
منشور في: 2009
الوصف
الملخص: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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