Genome-wide DNA methylation analysis in monozygotic twins identifies potential biomarkers of fasting plasma glucose

Purpose: An epigenome-wide association study (EWAS) was conducted to detect specific epigenetic variants potentially related to fasting plasma glucose (FPG) in middle-aged and elderly Chinese monozygotic twins.
Methods: Association between DNA methylation (DNAm) of single CpG and FPG was tested by applying generalized estimation equation in 52 twin pairs. Differentially methylated regions (DMRs) were identified by comb-P approach. Inference about Causation through Examination of Familial Confounding (ICE FALCON) was utilized to perform the causal inference. Candidate CpGs were quantified using Sequenom MassARRAY platform in a community population. Weighted gene co-expression network analysis (WGCNA) was conducted using gene expression data.
Results: The relationship between DNAm of 30 top CpGs and FPG reached P-value<1×10-6 level. Thirty-two DMRs within 24 genes, such as TLCD1, MRPS31P5, CASZ1 and CXADRP3, were identified. Causal relationship of 20 top CpGs within TLCD1, MZF1, PTPRN...