Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation: Meta-Analysis of Three Genome-Wide Association Studies
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Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation: Meta-Analysis of Three Genome-Wide Association Studies
| Title: | Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation: Meta-Analysis of Three Genome-Wide Association Studies |
| Author: |
Nolte, Ilja M.; Wallace, Chris; Newhouse, Stephen J.; Waggott, Daryl; Fu, Jingyuan; Soranzo, Nicole; Gwilliam, Rhian; Deloukas, Panos; Savelieva, Irina; Zheng, Dongling; Dalageorgou, Chrysoula; Farrall, Martin; Samani, Nilesh J.; Brown, Morris; Dominiczak, Anna; Lathrop, Mark; Zeggini, Eleftheria; Wain, Louise V.; Eijgelsheim, Mark; Pfeufer, Arne; Sanna, Serena; Arking, Dan E.; Asselbergs, Folkert W.; Spector, Tim D.; Carter, Nicholas D.; Jeffery, Steve; Tobin, Martin; Caulfield, Mark; Snieder, Harold; Munroe, Patricia B.; Jamshidi, Yalda; Connell, John; Newton-Cheh, Christopher Holmes; Rice, Kenneth Robert; de Bakker, Paul I Wen; Paterson, Andrew D.
Note: Order does not necessarily reflect citation order of authors. |
| Citation: | Nolte, Ilja M., Chris Wallace, Stephen J. Newhouse, Daryl Waggott, Jingyuan Fu, Nicole Soranzo, Rhian Gwilliam, 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. |
| Full Text & Related Files: |
2704957.pdf (243.1Kb; PDF) 
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| 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 Version: | doi:10.1371/journal.pone.0006138 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2704957/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:8160852 |
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