Type 2 diabetes (T2D) is one of the most common chronic
metabolic diseases characterized by
insulin resistance and the decrease of insulin secretion. Genetic variation can only explain part of the heritability of T2D, so there need new methods to detect the susceptibility genes of the disease. Epigenetics could establish the interface between the environmental factor and the T2D Pathological mechanism.
RESULTS: Based on the network theory and by combining epigenetic characteristics with human interactome, the weighted human DNA methylation network (WMPN) was constructed, and a T2D-related subnetwork (
TMSN) was obtained through T2D-related differentially methylated genes. It is found that
TMSN had a T2D specific network structure that non-fatal
metabolic disease causing genes were often located in the topological and functional periphery of network. Combined with
chromatin modifications, the weighted
chromatin modification network (WCPN) was built, and a T2D-related
chromatin modification pattern subnetwork was obtained by the
TMSN gene set. TCSN had a densely connected network community, indicating that
TMSN and TCSN could represent a collection of T2D-related epigenetic dysregulated sub-pathways. Using the cumulative hypergeometric test, 24 interplay modules of DNA methylation and
chromatin modifications were identified. By the analysis of gene expression in human T2D islet tissue, it is found that there existed genes with the variant expression level caused by the aberrant DNA methylation and (or)
chromatin modifications, which might affect and promote the development of T2D.
CONCLUSIONS: Here we have detected the potential interplay modules of DNA methylation and
chromatin modifications for T2D. The study of T2D epigenetic networks provides a new way for understanding the pathogenic mechanism of T2D caused by epigenetic disorders.