Fig. 1: Overview of the developed analytic framework and discovery of risk-associated TFs in breast cancer.

a A flow chart to illustrate the integrative analysis of ChIP-seq data (n = 113) and GWAS summary statistics of genetic variants data (n = 11 million) for breast cancer. b Barplots showing the numbers of detected binding peaks for each TF ChIP-seq data set in breast cancer cell lines. c Generalized mixed models constructed to evaluate the associations between the Chi-squared values (Y) and TF-DNA binding status of genetic variants of each TF, given LD blocks of variants to handle their dependence. d Quantile–quantile (QQ) plots of the association results of genetic variants in the whole genome (blue) and deflated genome (red) from the BCAC GWAS data. e A total of 22 identified TFs with genetic variation of TF-DNA bindings significantly associated with breast cancer risk. Top panel is for the whole genome and the bottom panel is for the deflated genome. f Distribution of genomic features (i.e., promoter, enhancer) for peaks of each TF. g Significant proportions of the host motifs and other known motifs for 13 TFs were detected based on motif enrichment analysis of their ChIP-seq peaks. h Genetic variations of TF-DNA bindings of TFs associated with breast cancer risk in BCAC data, stratified by motifs (i.e., host, non-host, and no motif). Of the 22 identified TFs, 13 with detected host motifs and the remaining ones without detected host motifs were presented in the top and bottom panels, respectively.