Mediation Analysis Demonstrates That Trans-eQTLs Are Often Explained by Cis-Mediation: A Genome-Wide Analysis among 1,800 South Asians (original) (raw)
Figure 1
Theoretical framework for _cis_-mediation of _trans_-eQTLs.
Panel (A) shows a causal diagram, in which a causal variant (SNPcausal) affects expression of a cis_-transcript (gene_cis) which in turn affects expression of a distant gene (gene_trans_). When SNPcausal is measured and is the strongest associated SNP (i.e., “lead SNP”) for both the _trans_- and _cis_-eQTL association signals, no other SNPs are involved in mediation analysis. Panel (B) shows the causal diagram underlying an eQTL mediation analysis when the causal variant is unmeasured or is not the lead SNP for both the trans_- and cis_-eQTL association signals. Thus, the lead SNP for gene_cis and gene_trans may be different, and are noted here as SNPlead-cis and SNPlead-trans, respectively. Solid lines represent causal effects, and dotted lines represent non-causal correlation, including linkage disequilibrium (LD).