Fig. 4. Exposure-to-mediator regulatory strength and number of mediators explaining mediation proportions (MPs).

a Summary of the correlations (R) between MP (red) and DNA methylation (DNAm)-to-transcript causal MR effects (${\widehat{\alpha }}_{\mathrm{EM}}^2$, dark green), distance between the DNAm site and transcription start site (TSS, light green) and number of mediators (N_med, blue). b Average MP through top transcript ($\widehat{\mathrm{MP}}$_top) of DNAm-trait pairs stratified according to the distance between the DNAm site and the TSS of the top transcript. All DNAm-trait pairs with at least one mediator were included (2069 pairs). c Average MR causal effects (${\widehat{\alpha }}_{\mathrm{EM}}^2$) of DNAm-transcript pairs stratified according to the distance between the DNAm site and the TSS. Unique DNAm-transcript mediator pairs across all DNAm-trait pairs were included (4743 pairs). d Average $\widehat{\mathrm{MP}}$_top of DNAm-trait pairs stratified according to DNAm-to-top transcript MR causal effect size ${\widehat{\alpha }}_{\mathrm{EM}}^2$. All DNAm-trait pairs with at least one mediator were included (2069 pairs). e Average $\widehat{\mathrm{MP}}$ of DNAm-trait pairs stratified according to the number of mediators. All DNAm-trait pairs with at least one mediator were included (2069 pairs). The reported p-values (P) for the corresponding Pearson correlations (R) arise from a two-sided t-test and were calculated between the two respective quantities on DNAm-trait/DNAm-transcript pairs prior stratification. Bin height represents mean within each bin and the error bars the corresponding standard deviations (number of evaluated pairs within each bin is indicated in parentheses). The red slope represents the regression fit between the bin’s positions and heights, and serves merely for visualization purposes.