• Figure 3.
    Download figureOpen in new tabFigure 3. DNA methylation associated to gene expression is not significantly allelic and can interact with genetic variation.

    (A) In green are depicted the distributions of allelic imbalance (i.e., absolute distance from the expected 0.5 ratio) of assayable heterozygote sites in eQTL genes of individuals that are homozygous (HOM) or heterozygous (HET) for the eQTL. The difference between distributions is significant in all cell-types with p<2.2 × 10−16, p=2.7 × 10−15 and p=3.0 × 10−8 in fibroblasts (F), LCLs (L) and T-cells (T), respectively (Wilcoxon test). This strongly indicates that allele specific expression is significantly driven by genetic variation. In purple are shown the distributions of allelic imbalance of assayable heterozygote sites in eQTM genes (excluding methylation sites affected by genetic variation) of individuals that are homomethylated (HOMOMETH, i.e., fully methylated, β-value > 0.7, or unmethylated β-value < 0.3) or semimethylated (SEMIMETH, i.e., β-value >0.3 and <0.7) for the eQTM site. The difference between distributions is not significant in any cell-type, with p=0.79, p=0.42 and p=0.49 in F, L, T, respectively. The difference between distributions of HET eQTLs and SEMIMETH eQTMs is significant in all cell-types with p=7.5 × 10−3, p=3.4 × 10−7, p=1.1 × 10−13, in F, L, T, respectively. The difference between distributions of IMPRINTED genes and HOMOMETH eQTMs is significant in all cell-types with p=6.9 × 10−34, p=9.7 × 10−4, p=8.5 × 10−5 in F, L, and T, respectively. This shows that allele specific expression is not significantly driven by DNA methylation that is not affected by genetic variation. (B) Using linear regression we tested the interaction term as shown in the illustrated formula for the effects of SNPs (green tick) and methylation sites (purple lollipop) on gene expression (black squared arrow and boxes). Qqplots illustrate the enrichment of low synergistic interaction observed p values (black), together with the 5th and 95th confidence limits based on expression permutations (gray) with respect to the expected uniform distribution.

    DOI: http://dx.doi.org/10.7554/eLife.00523.017