Fig. 3: Causal genes at the chromosome 7p15.3 locus associated with apoptotic cell death.

A The lead SNP rs2237324 at the 7p15.3 locus overlaps with peaks of ATAC-sequencing of vascular smooth muscle cells, peaks of H3K27Ac, and a candidate cis-regulatory element (cCRE) (ENCODE Accession: EH38E2540815). B Scatter plots of expression values of GSDME (left panel) and PALS2 (right panel) by genotype of the lead SNP rs2237324 at the 7p15.3 locus. Gray dots represent different vascular smooth muscle cell samples. β- and P values are from linear additive regression analysis. C Scatter plots of correlations of %DC4h (y-axis) with the expression values (x-axis) of GSDME (left panel) and PALS2 (right panel). Gray dots represent different vascular smooth muscle cell samples. Correlation coefficient (ϒ)- and P values are from Pearson correlation analysis. D LocusZoom plots showing colocalization of %DC4h cellular GWAS signal with GSDME eQTL signal (left panel) and PALS2 eQTL signal (right panel). The dots represent different single nucleotide polymorphisms (SNPs) and are colored according to their linkage disequilibrium values (r²). E Chromosome 7p15.3 regional plot showing %DC4h associations and eQTLs. Gray dots in the upper plot represent the P values for SNPs from the cellular GWAS of %DC4h, whilst diamonds represent the P values for genes from the summary-data-based Mendelian randomization (SMR) test. Filled diamonds highlight genes that were significant in the SMR test (P < 0.05). The genes that were significant in the SMR test are listed in red text, whilst the genes that were non-significant in the test are listed in blue text. The red crosses in the lower plots show the P values of eQTLs of GSDME and PALS2.