Fig. 2

Cis-mediation and inter-chromosomal interactions explain candidate trans-eQTL associations. A A candidate trans-eQTL may overlap with a cis-eQTL that regulates a proximal gene (cis-eGene), which may in turn regulate a distal gene (trans-eGene). B Roughly 62% of candidate trans-eQTLs colocalized with cis-eQTLs exhibit mediation effects. The number of candidate trans-eQTLs with positive mediation effect sizes is almost the same as those that are negative. C Cis- and trans-eGene pairs with evidence of cis-mediation display significant co-expression compared to both random pairs and those pairs that exhibit colocalization but not mediation. D Relative abundances of candidate trans-eQTLs that overlap with cis-eQTLs (left), colocalize with cis-eQTLs (middle), and exhibit mediation effects (right). Roughly 85% of trans-eGenes are also cis-eGenes, and ~17% of trans-eGenes have cis-mediators. E. Biological pathways associated with cis-eGenes that mediate candidate trans-eQTL associations are enriched for metabolic processes and transcriptional regulation. F Candidate trans-eQTL and eGene pairs tend to exhibit inter-chromosomal interactions more frequently than do random pairs. ACME, average causal mediation effects