Extended Data Fig. 4: Genomic locations and IPA analyses of HbA1c-associated genes.
From: DNA methylation mediates development of HbA1c-associated complications in type 1 diabetes
a, Genomic locations of HbA1c-associated CpGs and non-associated CpGs relative to Refseq genes depicted using pie charts. TSS, transcription start site; TSS1500, distal promoter region from 1,500 bp upstream of TSS to 200 bp upstream of TSS; TSS200, proximal promoter from 200 bp upstream of TSS to TSS; 5’UTR, 5’ untranslated region; 3’UTR, 3’ untranslated region; intergenic, genomic regions excluding TSS1500, TSS200 and gene body. b, Enriched canonical pathways (Benjamini-Hochberg adjusted P < 0.05) identified among annotated genes of HbA1c-associated CpGs. Right-tailed Fisher’s exact test was used in IPA analysis. Total of 143 unique annotated genes were used as input for IPA, and 141 genes after excluding 2 that did not match in the IPA database were finally included in the analysis. Pathway names are listed on the left with corresponding significance level in –log10 form presented in the middle as bar plot. The pathways labeled in red font are known to be associated with diabetes and its complications. HbA1c-associated genes identified in each pathway are shown on the right. Each row represents one pathway and each column represents one HbA1c-associated gene found in the enriched pathway. Red indicates the corresponding specific gene (with name shown on the top of the column) that is involved in the pathway specified on the left of the panel. The majority of them contain several NFAT pathway genes, including TGFBR2, GNAI2, CACNB1, PLCB4, MEF2D, TGFB2, ADCY7, PRKD1 and CACNA1A. c, Top network related to cellular growth, proliferation and embryonic development. The 24 HbA1c-associated genes labeled in red font are those identified to depict interactions with several proteins related to diabetes, its complications and insulin sensitivity including nuclear factor kappaB (NF-kB), protein kinaseB (PKB), phosphoinositide 3-kinase (PI3K), p38 mitogen-activated protein kinase (P38MAPK) and protein phosphatase2 catalytic (PPP2C) subunits. HbA1c-assoc CpGs: HbA1c-associated CpGs.
