Arrhythmias & electrophysiologyMeta-analysis
Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci
- Genome-wide association study with cross-ancestry meta-analysis
- case-control
- fine-mapping
- functional characterization
Authors' conclusion
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.
Study context
- Population
- Japanese participants with brugada syndrome (BrS) and controls; cross-ancestry meta-analysis with European genome-wide association studies (GWAS)Japanese: 940 cases, 1634 controls
- Comparison
- BrS cases vs controls, Japanese and European ancestries
- Outcome
- Novel BrS-associated loci and allelic effects across ancestries
Pooled result
As reported in the abstract
BrS-associated loci
- Japanese-specific GWAS: one novel locus near ZSCAN20
- P = 1.0 × 10-8
- Cross-ancestry meta-analysis: association signals
- 17
- Novel loci in cross-ancestry meta-analysis
- 6
- Consistent effect directions of 17 lead variants
- 94.1%; P for sign test = 2.7 × 10-4
- Correlation of allelic effects across ancestries
- Pearson's R = .91; P = 2.9 × 10-7
Further pooled results
| Outcome | OR (95% CI) | P value | |
|---|---|---|---|
| European-derived genetic risk score and BrS risk in Japanese population | 2.12 (1.94–2.31) | P = 1.2 × 10-61 | |
| 0.512Odds ratio (log scale) |
Functional characterization of CAMK2D lead variant
- Promotes alternative splicing, isoform switch of calmodulin kinase II-δ favouring pro-inflammatory/pro-death pathway
Original publication
Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci. Eur Heart J. Published 15 May 2024. doi:10.1093/eurheartj/ehae251
Summarised from the published abstract; every number is checked against it