Figure 4: Functional annotation of T1D-associated DVPs.

(a) Venn diagram showing the overlap of T1D-associated DVPs (FDR<0.001) across cell types. Although many of the identified DVPs were found to be cell type-specific, B cells and monocytes showed a substantial proportion of overlap. (b,c) Enrichment of T1D-associated DVPs at different epigenomic features and gene elements. Here, only DVPs at which the DNA methylation level was increased (hypermethylated; Δβ>0) in T1D twins compared with their healthy co-twins are shown. The enrichment is shown in relation to all 450K array probes that passed quality control. (d,e) The same analyses as shown in b and c, but for DVPs at which the DNA methylation level was reduced (hypomethylated; Δβ<0) in T1D twins. (f) Integration of T1D-associated DVPs with gene regulatory circuits in CD19⁺ B cells. The network was constructed using the corresponding genes of all T1D-associated hypomethylated DVPs that map to gene promoters and hypermethylated DVPs at gene bodies identified in B cells. The resulting network consisted of 297 genes connected via 906 regulatory edges. Three network modules were identified and are highlighted in different colours: Module 1 (n=61 genes) is shown in purple, module 2 (n=69) in green and module 3 (n=167) in orange. These modules were further characterized using functional enrichment analysis (Supplementary Table 2 and Supplementary Table 3). IGR, intergenic region; N, north, that is, upstream; S, south, that is, downstream; TSS200/1500, 200/1500, bp upstream of a transcription start site; UTR, untranslated region.