Common and rare susceptibility genetic variants predisposing to Brugada syndrome in Thailand

Mutations in SCN5A are rarely found in Thai patients with Brugada syndrome (BrS). Recent evidence suggested that common genetic variations may underlie BrS in a complex inheritance model. The purpose of this study was to find common and rare/low-frequency genetic variants predisposing to BrS in persons in Thailand. We conducted a genome-wide association study (GWAS) to explore the association of common variants in 154 Thai BrS cases and 432 controls. We sequenced SCN5A in 131 cases and 205 controls. Variants were classified according to current guidelines, and case-control association testing was performed for rare and low-frequency variants. Two loci were significantly associated with BrS. The first was near SCN5A/SCN10A (lead marker rs10428132; odds ratio [OR] 2.4; P = 3 × 10–10). Conditional analysis identified a novel independent signal in the same locus (rs6767797; OR 2.3; P = 2.7 × 10–10). The second locus was near HEY2 (lead marker rs3734634; OR 2.5; P = 7 × 10–9). Rare (minor allele frequency [MAF]