Figure 2: Integrative epigenomic profiling in HCASMC prioritizes CAD regulatory variants.
From: Integrative functional genomics identifies regulatory mechanisms at coronary artery disease loci
(a) Venn diagram of overlapping 5240 candidate CAD-associated variants (including those in high linkage disequilibrium at r2≥0.8) with HCASMC ATAC-seq open chromatin regions (n=323), H3K27ac ChIP-seq active enhancer regions (n=462) or TF binding via TCF21 or AP-1 ChIP-seq (n=193). Unique overlapping numbers shown for combined overlaps, respectively. (b) Forest plot depicting odds ratio (OR) of enrichment for CARDIoGRAMplusC4D (CAD), inflammatory bowel disease (IBD), ulcerative colitis (UC) or entire GWAS catalogue SNPs in individual or combined HCASMC data sets as calculated using the Fisher’s exact test. Dots represent mean OR and lateral lines represent 95% confidence intervals. (c) Histogram distribution of globally normalized GWAS SNPs in regions centred on HCASMC open chromatin regions within a 1-kb window. (d) Heatmap distribution of HCASMC open chromatin regions centred on CTCF motif (from JASPAR) within a 0.5-kb window (left panel). Hierarchical clustering heatmap showing distribution of ATAC-seq open chromatin, JUN or TCF21 ChIP-seq binding regions centred on 5,240 CARDIoGRAMplusC4D SNPs (right panels). (e) Two-dimensional scatter plot of GWAS SNPs in HCASMC open chromatin regions showing most significant enrichment for cardiovascular (CARDIoGRAMplusC4D and coronary heart), brain and autoimmune phenotypes in upper right quadrant. Data shown are representative of n=10 biological replicates in HCASMCs cultured under normal growth conditions.
