Properties of DNA methylation when associated to gene expression.

<p>(A) Number of all significant positive (pos-eQTMs) and negative (neg-eQTMs) correlations between DNA methylation and gene expression in fibroblasts (F), LCLs (L) and T-cells (T). A larger number of neg-eQTMs is found in all three cell-types, but an important part is composed of pos-eQTMs. (B) Percent of pos-eQTMs, neg-eQTMs and null sites that overlap with promoters, CpG island shores, CpG islands, gene bodies and enhancers. Pos-eQTMs are significantly depleted in promoter proximal regions in all cell-types. In most cases both positive and negative eQTMs are enriched for CpG island shores, gene bodies and enhancers, and depleted for CpG islands. One star indicates <i>P</i> < 0.05, two stars indicate <i>P</i> < 5E-04, Fisher’s exact test. (C) Correlation coefficients of eQTMs significant in both cell-types compared for all pair wise combinations of the three cell-types are plotted. The percentage of discordant cases (associations with opposite sign between any pair of cell-types) is indicated in the top left corner of each panel. Most eQTMs that are significant in any pair of cell-types have the same sign of association. (D) eQTM effect sizes are measured as the slope of the linear regression of expression given methylation on scaled values, and compared between cell-types for union of eQTMs. Black dots are significant eQTMs (same CpG-exon pair) in both the cell-types compared; orange, blue and purple dots are eQTMs significant only in fibroblast, LCL and T-cell, respectively, within the pair compared. Coefficient of determination <i>R</i>², reflecting the proportion of effect size variance in one cell-type explained by the other cell-type, is shown in the top left corner of each plot (<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004958#pgen.1004958.s001" target="_blank">S1 Table</a>). This shows that there is a large amount of tissue-specific effects for correlations between DNA methylation and gene expression.