A) Genome-wide evaluation of SNP-miRNA-mRNA associations. The genome-wide evaluation includes the identification of mRNA/miRNA eSNPs, and miRNA-mRNA expression pairs. B) Identification of CHD-related molecular relationships in CHD case-control samples. The overall analysis includes five steps. First, identify CHD differential mRNA signatures and mRNA co-expression module (this step and results were reported in our previous paper7). Second, identify differentially expressed miRNA signatures in CHD vs. controls. Third, identify miRNA-mRNA co-expression patterns in CHD cases and controls, and then identify differential miRNA-mRNA co-expression pairs between the two groups. Fourth, identify miRNAs correlated with CHD differential mRNA co-expression module. Fifth, integrate the CHD miRNA and mRNA sets identified in Step 1 to 4 with CHD GWAS as well as miRNA and mRNA eSNPs by the SNP set enrichment method35, in order to assess the directionality of causality.