Figure 3: DNA methylation variation in identical twin pairs discordant for T1D.

(a) Histogram of P-values for the identification of differentially methylated CpG positions (DMPs) between T1D-discordant MZ twin pairs in different immune effector cell types. DMPs were determined using a paired t test. (b) Histogram of P-values for the identification of T1D-associated differentially variable CpG positions (DVPs). DVPs were determined at an FDR of <0.001 using the algorithm iEVORA. (c) Bar plots showing the enrichment of DVPs in T1D twins compared with their healthy co-twins. While this hypervariability phenotype was found in all cell types (P<1 × 10⁻¹⁰⁰, binomial test), it was particularly pronounced in B cells. (d) Bar plots showing the odds ratios of the assessment of temporal stability of T1D-associated DVPs in an external data set of CD14⁺ and CD4⁺ cells derived from 12 disease-discordant MZ twin pairs generated on 27K arrays. Importantly, the identified DVPs in CD14⁺ and CD4⁺ cells replicated in a cell type-specific context. Stars denote statistical significance assessed using a one-tailed Fisher’s exact test: *P<1 × 10⁻² and **P<1 × 10⁻⁴. (e) Positive predictive values for the analyses shown in d. B, CD19⁺ B cells; M, CD14⁺CD16⁻ monocytes; T, CD4⁺ T cells.