DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Electrocardiographic traits. The EFO term electrocardiography, QT interval was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: electrocardiography, QT interval

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

JC Chambers, J Zhao, CM Terracciano, CR Bezzina, W Zhang, R Kaba, M Navaratnarajah, A Lotlikar, JS Sehmi, MK Kooner, G Deng, U Siedlecka, S Parasramka, I El-Hamamsy, MN Wass, LR Dekker, JS de Jong, MJ Sternberg, W McKenna, NJ Severs, R de Silva, AA Wilde, P Anand, M Yacoub, J Scott, P Elliott, JN Wood, JS Kooner

TITLE:

Genetic variation in SCN10A influences cardiac conduction.

JOURNAL:

Nature genetics Feb 2010, Vol 42, pp. 149-52

ABSTRACT:

To identify genetic factors influencing cardiac conduction, we carried out a genome-wide association study of electrocardiographic time intervals in 6,543 Indian Asians. We identified association of a nonsynonymous SNP, rs6795970, in SCN10A (P = 2.8 x 10(-15)) with PR interval, a marker of cardiac atrioventricular conduction. Replication testing among 6,243 Indian Asians and 5,370 Europeans confirmed that rs6795970 (G>A) is associated with prolonged cardiac conduction (longer P-wave duration, PR interval and QRS duration, P = 10(-5) to 10(-20)). SCN10A encodes Na(V)1.8, a sodium channel. We show that SCN10A is expressed in mouse and human heart tissue and that PR interval is shorter in Scn10a(-/-) mice than in wild-type mice. We also find that rs6795970 is associated with a higher risk of heart block (P < 0.05) and a lower risk of ventricular fibrillation (P = 0.01). Our findings provide new insight into the pathogenesis of cardiac conduction, heart block and ventricular fibrillation. PUBMED: 20062061
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