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

Pattarapong Makarawate, Charlotte Glinge, Apichai Khongphatthanayothin, Roddy Walsh, John Mauleekoonphairoj, Montawatt Amnueypol, Somchai Prechawat, Wanwarang Wongcharoen, Rungroj Krittayaphong, Alisara Anannab, Peter Lichtner, Thomas Meitinger, Fleur V.Y. Tjong, Krystien V.V. Lieve, Ahmad S. Amin, Dujdao Sahasatas, Tachapong Ngarmukos, Duangdao Wichadakul, Sunchai Payungporn, Boosamas SutjapornPharawee Wandee, Yong Poovorawan, Jacob Tfelt-Hansen, Michael W.T. Tanck, Rafik Tadros, Arthur A.M. Wilde, Connie R. Bezzina, Gumpanart Veerakul, Koonlawee Nademanee

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Background: 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. Objective: The purpose of this study was to find common and rare/low-frequency genetic variants predisposing to BrS in persons in Thailand. Methods: 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. Results: 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] <0.0001) coding variants in SCN5A were found in 8 of the 131 cases (6.1% in cases vs 2.0% in controls; P = .046; OR 3.3; 95% confident interval [CI] 1.0–11.1), but an enrichment of low-frequency (MAF<0.001 and >0.0001) variants also was observed in cases, with 1 variant (SCN5A: p.Arg965Cys) detected in 4.6% of Thai BrS patients vs 0.5% in controls (P = 0.015; OR 9.8; 95% CI 1.2–82.3). Conclusion: The genetic basis of BrS in Thailand includes a wide spectrum of variant frequencies and effect sizes. As previously shown in European and Japanese populations, common variants near SCN5A and HEY2 are associated with BrS in the Thai population, confirming the transethnic transferability of these 2 major BrS loci.

Original languageEnglish
Pages (from-to)2145-2153
Number of pages9
JournalHeart Rhythm
Volume17
Issue number12
DOIs
StatePublished - Dec 2020
Externally publishedYes

Keywords

  • Brugada syndrome
  • Genetics
  • Genome-wide association study
  • SCN5A
  • Thailand

Fingerprint

Dive into the research topics of 'Common and rare susceptibility genetic variants predisposing to Brugada syndrome in Thailand'. Together they form a unique fingerprint.

Cite this