51. Common genetic variation near the phospholamban gene is associated with cardiac repolarisation
- Author
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Nolte, I.M. (Ilja), Wallace, C. (Chris), Newhouse, S.J. (Stephen), Waggott, D. (Daryl), Fu, J. (Jingyuan), Soranzo, N. (Nicole), Gwilliam, R. (Rhian), Demissie, S. (Serkalem), Savelieva, I. (Irina), Zheng, D. (Dongling), Dalageorgou, C. (Chrysoula), Farrall, M. (Martin), Samani, N.J. (Nilesh), Connell, J. (John), Brown, M.J. (Morris), Dominiczak, A. (Anna), Lathrop, M. (Mark), Zeggini, E. (Eleftheria), Wain, L.V. (Louise), Newton-Cheh, C. (Christopher), Eijgelsheim, M. (Mark), Rice, K. (Kenneth), Bakker, P.I.W. (Paul) de, Pfeufer, A. (Arne), Sanna, S. (Serena), Arking, D.E. (Dan), Asselbergs, F.W. (Folkert), Spector, T.D. (Timothy), Carter, N.D. (Nicholas), Jeffery, S. (Steve), Tobin, M. (Martin), Caulfield, M. (Mark), Snieder, H. (Harold), Paterson, A.D. (Andrew), Munroe, P. (Patricia), Jamshidi, Y. (Yalda), Nolte, I.M. (Ilja), Wallace, C. (Chris), Newhouse, S.J. (Stephen), Waggott, D. (Daryl), Fu, J. (Jingyuan), Soranzo, N. (Nicole), Gwilliam, R. (Rhian), Demissie, S. (Serkalem), Savelieva, I. (Irina), Zheng, D. (Dongling), Dalageorgou, C. (Chrysoula), Farrall, M. (Martin), Samani, N.J. (Nilesh), Connell, J. (John), Brown, M.J. (Morris), Dominiczak, A. (Anna), Lathrop, M. (Mark), Zeggini, E. (Eleftheria), Wain, L.V. (Louise), Newton-Cheh, C. (Christopher), Eijgelsheim, M. (Mark), Rice, K. (Kenneth), Bakker, P.I.W. (Paul) de, Pfeufer, A. (Arne), Sanna, S. (Serena), Arking, D.E. (Dan), Asselbergs, F.W. (Folkert), Spector, T.D. (Timothy), Carter, N.D. (Nicholas), Jeffery, S. (Steve), Tobin, M. (Martin), Caulfield, M. (Mark), Snieder, H. (Harold), Paterson, A.D. (Andrew), Munroe, P. (Patricia), and Jamshidi, Y. (Yalda)
- 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.
- Published
- 2009
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