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

Nolte, IM; Wallace, C; Newhouse, SJ; Waggott, D; Fu, J; Soranzo, N; Gwilliam, R; Deloukas, P; Savelieva, I; Zheng, D; Dalageorgou, C; Farrall, M; Samani, NJ; Connell, J; Brown, M; Dominiczak, A; Lathrop, M; Zeggini, E; Wain, LV; Newton-Cheh, C; Eijgelsheim, M; Rice, K; de Bakker, PI; Pfeufer, A; Sanna, S; Arking, DE; Asselbergs, FW; Spector, TD; Carter, ND; Jeffery, S; Tobin, M; Caulfield, M; Snieder, H; Paterson, AD; Munroe, PB; Jamshidi, Y

doi:10.1371/journal.pone.0006138

journal article

Dokumenttyp:: Journal Article; Meta-Analysis; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Autor(en):: Nolte, IM; Wallace, C; Newhouse, SJ; Waggott, D; Fu, J; Soranzo, N; Gwilliam, R; Deloukas, P; Savelieva, I; Zheng, D; Dalageorgou, C; Farrall, M; Samani, NJ; Connell, J; Brown, M; Dominiczak, A; Lathrop, M; Zeggini, E; Wain, LV; Newton-Cheh, C; Eijgelsheim, M; Rice, K; de Bakker, PI; Pfeufer, A; Sanna, S; Arking, DE; Asselbergs, FW; Spector, TD; Carter, ND; Jeffery, S; Tobin, M; Caulfield, M; Snieder, H; Paterson, AD; Munroe, PB; Jamshidi, Y
Titel:: 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.
Zeitschriftentitel:: PLoS ONE
Jahr:: 2009
Band / Volume:: 4
Heft / Issue:: 7
Seitenangaben Beitrag:: e6138
Sprache:: eng
Volltext / DOI:: doi:10.1371/journal.pone.0006138
PubMed:: http://view.ncbi.nlm.nih.gov/pubmed/19587794
Print-ISSN:: 1932-6203
TUM Einrichtung:: Institut für Humangenetik
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