Extended Data Fig. 2: Annotation of the chromosome 18 locus.

Top panel, Locus Zoom plot of BrS associated variant at the chromosome 18 locus based on the meta-analysis data. –log₁₀ P-values are shown along the left y-axis, and the right y-axis corresponds to recombination rate, plotted as a blue line. The x-axis indicates chromosomal position. The lead variant at each association signal is shown as a purple diamond. Other variants are colored according to their correlation (r²) with the lead variant (see legend). Middle panel, Graphic representation of the chromosome 18 locus displaying the following annotations: genomic coordinates (hg19), topologically associated domains (TAD)⁶⁹; region containing SNPs in linkage disequilibrium with the lead SNP at the locus (red bar, LD, r² ≥ 0.6); genes located in the locus; chromatin interactions identified in human left ventricular tissue⁵¹ overlapping the association signal (± 40 kb corresponding to the Hi-C dataset resolution), and expression quantitative trait loci (eQTL) reported in GTEx²⁰ for human left ventricular tissue. Bottom left panel, eQTL violin plot from GTEx displaying significant association between the lead SNP of the chromosome 18 locus and the expression of MAPRE2 within the cardiac ventricular tissue. The number of left ventricular heart samples per genotype is shown in parentheses. In the box plots, the middle line shows the median value of the expression of each genotype, while the violin plots show the distribution. Bottom right panel, Locus compare plot depicting SNPs at the chromosome 18 locus. The eQTL –log₁₀ P-value is plotted on the y-axis, and the BrS GWAS meta-analysis –log₁₀ P-value is plotted on the x-axis. SNPs are colored according to their degree of linkage disequilibrium (r²), with the lead BrS associated variant highlighted as a purple diamond. eQTL, expression quantitative trait locus. Note that a different scale is used in the top and middle panels.