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Study Report - Meta-analysis of cardiac repolarisation (HGVST365)| HGVbaseG2P identifier | HGVST365 | ||||||||||||||||||||
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| Study name | Meta-analysis of cardiac repolarisation | ||||||||||||||||||||
| Phenotype(s) tested | Cardiac repolarisation |
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| Study design | Quantitative trait analysis with replication | ||||||||||||||||||||
| Genotype Platforms |
Affymetrix & Illumina ~2,399,142 | ||||||||||||||||||||
| 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. | ||||||||||||||||||||
| Submission information |
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| Cross-references |
NHGRI GWAS catalog study annotation for HGVST365 |
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| Background | Not supplied | ||||||||||||||||||||
| Objectives | Not supplied | ||||||||||||||||||||
| Key results | Not supplied | ||||||||||||||||||||
| Conclusions | Not supplied | ||||||||||||||||||||
| Reason for study size | Not supplied | ||||||||||||||||||||
| Study power | Not supplied | ||||||||||||||||||||
| Sources of bias | Not supplied | ||||||||||||||||||||
| Limitations | Not supplied | ||||||||||||||||||||
| Acknowledgements | Not supplied | ||||||||||||||||||||
| Other citations |
Hindorff LA, Sethupathy P, Junkins HA et al.
Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proceedings of the National Academy of Sciences U S A. 2009 May 27
Nolte IM, Wallace C, Newhouse SJ et al.
Common genetic variation near the phospholamban gene is associated with cardiac repolarisation: meta-analysis of three genome-wide association studies. PloS one 2009 |
