Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci

Brugada syndrome (BrS) is a rare cardiac rhythm disorder with a high risk of sudden cardiac death. The disease is more frequently seen in Asian populations compared to Europeans where the condition is also more lethal and related to cardiac arrhythmias, in Asian patients. Prior studies with the aim to reveal the genetic basis of Brugada syndrome, have primarily been performed in individuals of European descent, whereas this study looked to compare the genetic basis between Brugada syndrome patients of both Asian and European descent. The focus was particularly on the potential role of genetic variations (genetic differences) that are often found in the general population which may potentially play a modulatory role (how they can modify or adjust how other genes function).

The study was initially conducted in Japanese participants, involving 940 patients with Brugada syndrome and 1634 controls. This initial study was followed by a much larger study where samples from Japanese and European individuals were combined (total of 3760 cases and 11635 controls).

In both studies some newly discovered genetic loci (location of the gene within a chromosome) were identified, which provides new insight into the origin of Brugada syndrome. One of these new loci points to a role of inflammation/cell death. Overall, it appeared that the genetic basis of Brugada syndrome was rather similar between individuals from Asian and European descent. This means that other factors, i.e. other than genetic factors, must be responsible for the differences in epidemiology and clinical appearance between ethnical groups. The hope is that with a better understanding of these differences better personalised risk prediction will become available. In addition, further investigation in the new leads will follow.

 

Translated by Arthur Wilde and Lorraine McGlinchey

Ishikawa T, Masuda T, Hachiya T, Dina C, Simonet F, Nagata Y, Tanck MWT, Sonehara K, Glinge C, Tadros R, Khongphatthanayothin A, Lu TP, Higuchi C, Nakajima T, Hayashi K, Aizawa Y, Nakano Y, Nogami A, Morita H, Ohno S, Aiba T, Juárez CK, Mauleekoonphairoj J, Poovorawan Y, Gourraud JB, Shimizu W, Probst V, Horie M, Wilde AAM, Redon R, Juang JJ, Nademanee K, Bezzina CR, Barc J, Tanaka T, Okada Y, Schott JJ, Makita N. Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci. Eur Heart J 45, 2320-2332, 2024. PMID: 38747976, https://doi.org/10.1093/eurheartj/ehae251