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 Brugada syndrome. The EFO term Brugada syndrome 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: Brugada syndrome

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

CR Bezzina, J Barc, Y Mizusawa, CA Remme, JB Gourraud, F Simonet, AO Verkerk, PJ Schwartz, L Crotti, F Dagradi, P Guicheney, V Fressart, A Leenhardt, C Antzelevitch, S Bartkowiak, M Borggrefe, R Schimpf, E Schulze-Bahr, S Zumhagen, ER Behr, R Bastiaenen, J Tfelt-Hansen, MS Olesen, S Kääb, BM Beckmann, P Weeke, H Watanabe, N Endo, T Minamino, M Horie, S Ohno, K Hasegawa, N Makita, A Nogami, W Shimizu, T Aiba, P Froguel, B Balkau, O Lantieri, M Torchio, C Wiese, D Weber, R Wolswinkel, R Coronel, BJ Boukens, S Bézieau, E Charpentier, S Chatel, A Despres, F Gros, F Kyndt, S Lecointe, P Lindenbaum, V Portero, J Violleau, M Gessler, HL Tan, DM Roden, VM Christoffels, H Le Marec, AA Wilde, V Probst, JJ Schott, C Dina, R Redon

TITLE:

Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death.

JOURNAL:

Nature genetics Sep 2013, Vol 45, pp. 1044-9

ABSTRACT:

Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases. Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) and near the HEY2 gene (rs9388451). Independent replication confirmed both signals (meta-analyses: rs10428132, P = 1.0 × 10(-68); rs9388451, P = 5.1 × 10(-17)) and identified one additional signal in SCN5A (at 3p21; rs11708996, P = 1.0 × 10(-14)). The cumulative effect of the three loci on disease susceptibility was unexpectedly large (Ptrend = 6.1 × 10(-81)). The association signals at SCN5A-SCN10A demonstrate that genetic polymorphisms modulating cardiac conduction can also influence susceptibility to cardiac arrhythmia. The implication of association with HEY2, supported by new evidence that Hey2 regulates cardiac electrical activity, shows that Brugada syndrome may originate from altered transcriptional programming during cardiac development. Altogether, our findings indicate that common genetic variation can have a strong impact on the predisposition to rare diseases. PUBMED: 23872634
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