Extended Data Fig. 6: Enrichment of chromatin (epigenetic) states at HbA1c-associated CpG sites in blood cells.
From: DNA methylation mediates development of HbA1c-associated complications in type 1 diabetes
a, Enrichment of chromatin states in each cell-type at the 186 HbA1c-associated CpGs. For each cell-type, the percentage of CpGs located in genomic regions enriched with 18 chromatin states (labeled under the plots) at HbA1c-associated CpGs (dark bars) versus all CpGs covered by the EPIC array (white bars) in 4 major blood cell-types are shown side-by-side in the bar plots. Right-tailed Fisher’s exact tests were conducted to identify the significance of enrichment of each state in 186 HbA1c-associated CpGs relative to all the 815,246 non HbA1c-associated CpGs reliably covered by EPIC array. States with significant enrichment in at least one cell-type are highlighted with colored background/shading: green for transcription-related (Tx and TxWk) and yellow for enhancer-related states (EnhG1, EnhG2, EnhA1, EnhA2 or EnhWk). P values listed on top of each significantly enriched state.****P < 5 × 10−8; ***P < 5 × 10−5; **P < 5 × 10−3 and *P < 5 × 10−2. The other states are shown in alternating grey and white shades for better visualization. b, Enrichment of enhancer- or transcription-related states across 4 different cell-types in HbA1c-associated CpGs versus all CpGs. The states for each plot are shown in the heading. P-values were determined using same tests and sample sizes as in panel a. c, Comparison of heatmaps of 15 chromatin states in 6 blood cell-types (top) with heatmaps of 18 states at 4 blood cell-types (bottom) at HbA1c-associated CpGs. These states are defined by the NIH Roadmap Epigenomics Program. Unsupervised hierarchical analysis was performed on data from 15 states and visualized in the top panel using colours depicted in the boxed legend for 15 states (bottom left). 18-chromatin states at HbA1c-associated CpGs, presented in the same order as 15 states, are shown in the lower panel with corresponding colour legends in the bottom right box. Each row represents one cell-type and each column, one CpG. HbA1c-assoc CpGs: HbA1c-associated CpGs.
