To evaluate whether the trans-eQTLs could be explained by direct or indirect TF action25, protein–protein interactions (PPI)26 or co-regulation between cis- and trans-eQTL genes, we conducted enrichment analyses (Supplementary Note, Supplementary Figure 9, Figure 3b). Cis- and trans-eQTL genes emerging from the same SNP were 1.28-fold enriched by TF - TF target pairs, compared to all other gene pairs (P=4.0×10−21; two-sided Fisher’s exact test; Supplementary Figure 8). When we included additional local genes into the trans-eQTL loci with Pascal27, (Supplementary Note, Supplementary Figure 10) we observed a 1.40-fold enrichment for TFs (P=5.6×10−36; two-sided Fisher’s exact test; Figure 3b). There was also enrichment for genes co-regulated with known TFs (1.38-fold, P=5.8×10−72; two-sided Fisher’s exact test; Figure 3b), genes co-regulated with known target genes (3.57-fold, P<1.0×10−308; two-sided Fisher’s exact test; Figure 3b), and genes co-regulated with both (4.37-fold, P<1.0×10−308; two-sided Fisher’s exact test; Figure 3b), suggesting indirect consequences of transcriptional regulation. We observed a strong 22.3-fold enrichment (P<1.0×10−308; two-sided Fisher’s exact test) of co-regulated gene pairs and a 1.45-fold enrichment of protein–protein interaction (PPI)26 pairs (P=3.5×10−17; two-sided Fisher’s exact test), including co-regulated
