| Title: |
Common Genetic Variation Near the Phospholamban Gene Is Associated with Cardiac Repolarisation: Meta-Analysis of Three Genome-Wide Association Studies |
| Authors: |
Nolte, IM; Wallace, C; Newhouse, SJ; Waggott, D; Fu, JY; Soranzo, N; Gwilliam, R; Deloukas, P; Savelieva, I; Zheng, DL; 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, PIW; 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; Wellcome Trust Case Control Consor; DCCT EDIC Res Grp; QTGEN Consortium; QTSCD Consortium |
| Source: |
PLOS ONE , 4 (7) , Article e6138. (2009) |
| Publisher Information: |
PUBLIC LIBRARY SCIENCE |
| Publication Year: |
2009 |
| Collection: |
University College London: UCL Discovery |
| Description: |
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 x 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 x 10-(83)) and the phospholamban (PLN) gene (P = 1.9 x 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. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/1332675/1/1332675.pdf; https://discovery.ucl.ac.uk/id/eprint/1332675/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/1332675/1/1332675.pdf; https://discovery.ucl.ac.uk/id/eprint/1332675/ |
| Rights: |
open |
| Accession Number: |
edsbas.5CBF0B61 |
| Database: |
BASE |