Figure 5. Intersection of QTLs for CpG and mRNA traits.

Plots shown for each tissue region; cerebellum, frontal cortex, pons and temporal cortex. Per tissue for every pairing of CpG site and mRNA transcript where the CpG was within a CpG island and within 1Mb of the mRNA TSS and both the CpG and mRNA have a significant cis QTL; i.e. a triplet is formed between SNP, mRNA and CpG, where the SNP was significantly correlated in cis with either the CpG or mRNA of the CpG-mRNA cis pairs under consideration. For these triplets we plotted the eQTL R² (X axis) and the methQTL R² (Y axis). The R² values are shifted into one of four quadrants (without changing the effect size) based on the positive and negative combinations of correlations for the eQTLs and methQTLs. A positive correlation with mRNA means that the level of expression is increased with the minor allele of the SNP and a negative correlation means that the mRNA expression level is decreased with the minor allele of the SNP. For CpGs a positive correlation implies that the level of methylation is increased at a CpG site with the minor allele and a negative correlation implies that the level of methylation is decreased with the minor allele. The top-left quadrant contains negative eQTL and positive methQTL correlations. The top-right quadrant contains eQTLs and methQTLs where the correlation was positive in both. The bottom-left quadrant contains eQTLs and methQTLs where the correlation was negative in both. The bottom-right quadrant contains positive eQTL and negative methQTL correlations. The triplets are plotted as circles where the radius of the circle represent the R² value between the CpG site and mRNA transcript. The color of circle represents the distance between the CpG site and the mRNA TSS, where red indicates that the CpG site is close and upstream to the mRNA TSS; blue indicates that the CpG site is close to the mRNA TSS but downstream; and black indicates that the CpG site is farther from the mRNA TSS both up or downstream. Triplets that fall along the main diagonals are those where a significant methQTL and eQTL are present; the CpG and mRNA pairs for these triplets are closer together and have a larger R² between the CpG and mRNA. Triplets that are on or close to the X axis are those where there is a significant eQTL but a lack of signal for the methQTL, likewise the items that are on or close to the Y axis are those with a significant methQTL and a lack of signal for the eQTL.