Nolte, I. M. et al. (2009) Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies. PLoS ONE, 4(7), e6138. (doi: 10.1371/journal.pone.0006138)
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Publisher's URL: http://dx.doi.org/10.1371/journal.pone.0006138
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<sup>−6</sup>. 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<sup>−83</sup>) and the phospholamban (PLN) gene (P = 1.9×10<sup>−29</sup>). 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.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Connell, Professor John and Dominiczak, Professor Anna |
Authors: | Nolte, I. M., Wallace, C., Newhouse, S. J., Waggott, D., Fu, J., Soranzo, N., Gwilliam, R., Deloukas, P., Savelieva, I., Zheng, D., Dalageorgou, C., Farrall, M., Samani, N. J., Connell, J., Brown, M., Dominiczak, A., Lathrop, M., Zeggini, E., Wain, L. V., Newton-Cheh, C., Eijgelsheim, M., Rice, K., de Bakker, P. I.W., Pfeufer, A., Sanna, S., Arking, D. E., Asselbergs, F. W., Spector, T. D., Carter, N. D., Jeffery, S. J., Tobin, M., Caulfield, M., Snieder, H., Paterson, A. D., Munroe, P. B., and Jamshidi, Y. |
College/School: | College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
Journal Name: | PLoS ONE |
Publisher: | Public Library of Science |
ISSN: | 1932-6203 |
ISSN (Online): | 1932-6203 |
Published Online: | 09 January 2009 |
Copyright Holders: | Copyright © 2009 Public Library of Science |
First Published: | First published in PLoS ONE 4(7):e6138 |
Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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