Figure 4. Epigenetic mediation of eQTLs.

(A) Sharing of SNPs between eQTLs, mQTLs, and haQTLs. 2,305,942 SNPs tested for all molecular phenotypes are considered. (B) Three models relating SNPs (s), epigenetic features (methylation/histone acetylation, m/h) and gene expression (g): i) independent model (IM) where effects of SNPs on epigenetic features and transcripts are unrelated, ii) epigenetic mediation model (EM) where epigenetic features mediate the effects of SNPs on gene expression, and iii) transcription mediation model (TM) where the effects of SNPs on epigenetics is mediated through its effect on gene expression. The causal inference test was used for assessing mediation³⁵. (C) Proportion of shared xQTL SNPs that are consistent with each model. (D) Expression level of IL1RL1 vs. number of minor alleles present for rs13015714, which is a shared xQTL SNP that impacts IL1RL1 expression and nearby DNA methylation and histone acetylation levels. The red line corresponds to the mean. The yellow region corresponds to the 95% confidence interval of the mean. The edges of the blue region correspond to ±1 standard deviation. The SNP effect disappears after regressing out the effect of the mQTL probes and haQTL peaks associated with rs13015714 from IL1RL1 expression. (E) Association between IL1RL1 expression and the levels of its associated methylation probes and acetylation peaks. Colors indicate the genotype of rs13015714: minor allele homozygotes (yellow), heterozygotes (green), major allele homozygotes (blue).