Figure 1: PWAS screen systematically identified allele-specific TF binding at the selected CRC risk loci.

(a) Allele-specific binding of the 731 candidate TFs at the 116 CRC risk loci. Chromatin environment of the 116 SNPs was described by DHS of these loci in the 15 fetal large intestine tissues and 12 CRC cell lines, and histone modifications (H3K4me3, H3K4me1 and H3K27ac) within ±1 kb regions around these loci in the LoVo and HCT116 cell lines. The TFs with P-value<10−30 and absolute Log2(fold change)>3 was listed in the bubble plot. Bubble size represents −Log10(P-values) of the interactors in the pull-down screen (n=2 pulldowns per SNP, P-values: A/B significance test). (b) Pathway annotation of the 731 TFs (HR, gonadotropin-releasing hormone receptor pathway; WNT/PDGF/CCKR/transforming growth factor (TGF)-β, Wnt/PDGF/Cholecystokinin/TGF-β signalling pathways). (c) TF–SNP interactions ranked by fold changes in the PWAS screen and DHS at the SNP loci. Bubble size indicates the −Log10(P-values) of the TF–SNP interactions (n=2 pulldowns per SNP, red and blue bubbles: P-value<0.05, Z-test). (d) The top three candidate TF–SNP interactions (n=2 pulldowns per SNP, red and blue dots: P-values<0.01, A/B significance test).