Extended Data Fig. 8: Epigenetic QTLs overlap with genetic variants associated with immune-related diseases.

(A) Summary of colocalization results for duplicated immune related diseases (11 diseases were investigated through 14 GWAS). Points represent the number of significant hits defined as PP3 + PP4 > 0.5 and PP4/(PP3 + PP4) > 0.8 in either condition. (B) Summary of PrediXcan results. Each point represents the total number of genes (Bonferroni corrected p = 0.05) associated with the disease trait in either condition. A gene is only counted once even if multiple peaks are associated with the gene. (C) Schematic depicting the proposed hypothesis that epigenetic QTL may act as a proxy for genetic variation that under particular environmental conditions has an impact on gene expression levels. Blue boxes represent gene exons and green peaks represent ATACseq peaks. A genetic variant at the QTL ___location impacts TF binding, such that differential binding of the TF is associated with variation in chromatin accessibility (that is, an caQTL). If the activity of this enhancer requires the recruitment of an additional TF (here labelled “environment-induced TF”) only induced in response to specific environmental/developmental conditions, the caQTL will not be associated with variation in gene expression levels. Yet, this caQTL will be a proxy for a genetic variant that on the “right environment” will ultimately be associated with an eQTL. Under this model, epigenetic QTLs that colocalize with GWAS variants (but not with eQTLs) can be thought of as a means to identify genetic variants that have an impact on gene expression in a yet unmeasured environment. Created with BioRender.com.