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arrhythmic events in Asians than in Europeans. Genome-wide association studies (GWAS) have revealed its polygenic architecture mainly in European populations. The aim of this study was to identify novel BrS-associated loci and to compare allelic effects across ancestries.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A GWAS was conducted in Japanese participants, involving 940 cases and 1634 controls, followed by a cross-ancestry meta-analysis of Japanese and European GWAS (total of 3760 cases and 11 635 controls). The novel loci were characterized by fine-mapping, gene expression, and splicing quantitative trait associations in the human heart.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The Japanese-specific GWAS identified one novel locus near ZSCAN20 (P = 1.0 \u00d7 10\u22128), and the cross-ancestry meta-analysis identified 17 association signals, including six novel loci. The effect directions of the 17 lead variants were consistent (94.1%; P for sign test = 2.7 \u00d7 10\u22124), and their allelic effects were highly correlated across ancestries (Pearson\u2019s R = .91; P = 2.9 \u00d7 10\u22127). The genetic risk score derived from the BrS GWAS of European ancestry was significantly associated with the risk of BrS in the Japanese population [odds ratio 2.12 (95% confidence interval 1.94\u20132.31); P = 1.2 \u00d7 10\u221261], suggesting a shared genetic architecture across ancestries. Functional characterization revealed that a lead variant in CAMK2D promotes alternative splicing, resulting in an isoform switch of calmodulin kinase II-\u03b4, favouring a pro-inflammatory\/pro-death pathway.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This study demonstrates novel susceptibility loci implicating potentially novel pathogenesis underlying BrS. Despite differences in clinical expressivity and epidemiology, the polygenic architecture of BrS was substantially shared across ancestries.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehae251","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T14:49:56Z","timestamp":1715784596000},"page":"2320-2332","source":"Crossref","is-referenced-by-count":25,"title":["Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci"],"prefix":"10.1093","volume":"45","author":[{"given":"Taisuke","family":"Ishikawa","sequence":"first","affiliation":[{"name":"Omics Research Center, National Cerebral and Cardiovascular Center , Suita , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuo","family":"Masuda","sequence":"additional","affiliation":[{"name":"Department of Statistical Genetics, Osaka University Graduate School of Medicine , Suita , 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