Figure 5.

5modC and 5hmC methylation biology in imprinting, aging, and sex specificities

(A) Heatmap showing beta values across all tissues (columns) for CpGs (rows) with intermediate 5modC levels (0.3–0.7), suggestive of monoallelic DNA methylation.

(B) Mean beta values for intermediately modified probes for six representative genes, showing patterns resembling known imprinting genes.

(C) Manhattan plot of aging 5hmC EWAS signals (bottom) and scatterplots for representative age-associated 5hmC CpGs (top).

(D) Enrichment of 10 epigenetic clocks in age-associated 5hmC probes. Probes are ranked according to the p value of the 5hmC-age association. Representative clocks are shown on the right.

(E) Age prediction using clocks trained on 5hmC (top left), 5mC (top right), 5modC (bottom left), and Horvath clock (bottom right); x axis: self-reported age, y axis: predicted age. Plots show Pearson correlation coefficients, p value, and mean absolute error of predictions.

(F) Boxplots of 5modC and 5hmC beta values at representative autosomal CpGs with sex-specific methylation.