http://dx.doi.org/10.1371/journal.pone.0006138
pubmed: 19587794
scopus: 67650280679
Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: Meta-analysis of three genome-wide association studies
2009-07-09
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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.
- study
- interval
- qt interval
- qt interval duration
- research
- heart
- association
- institute
- twinsuk
- /edic
- cohort
- dcct /edic cohorts
- university
- individual
- variant
- result
- duration
- phospholamban
- nos 1ap
- diabetes
