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Title: Common and rare susceptibility genetic variants predisposing to Brugada syndrome in Thailand
Authors: 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 Sutjaporn
Pharawee Wandee
Yong Poovorawan
Jacob Tfelt-Hansen
Michael W.T. Tanck
Rafik Tadros
Arthur A.M. Wilde
Connie R. Bezzina
Gumpanart Veerakul
Koonlawee Nademanee
Københavns Universitet
Chulalongkorn University
Helmholtz Center Munich German Research Center for Environmental Health
Bumrungrad International Hospital
Khon Kaen University
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Institut de Cardiologie de Montreal
Faculty of Medicine, Siriraj Hospital, Mahidol University
Universiteit van Amsterdam
Chiang Mai University
Bangkok Heart Hospital
European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart (ERN GUARDHEART
Central Chest Institute of Thailand
Keywords: Medicine
Issue Date: 1-Dec-2020
Citation: Heart Rhythm. Vol.17, No.12 (2020), 2145-2153
Abstract: © 2020 Heart Rhythm Society 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.
ISSN: 15563871
Appears in Collections:Scopus 2020

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