Blood DNA methylation markers associated with type 2 diabetes, fasting glucose, and HbA1c levels: An epigenome-wide association study in 316 adult twin pairs

DNA methylation plays an important role in the development and etiology of type 2 diabetes; however, few epigenomic studies have been conducted on twins. Herein, a two-stage study was performed to explore the associations between DNA methylation and type 2 diabetes, fasting plasma glucose, and HbA1c. DNA methylation in 316 twin pairs from the Chinese National Twin Registry (CNTR) was measured using Illumina Infinium BeadChips. In the discovery sample, the results revealed that 63 CpG sites and 6 CpG sites were significantly associated with fasting plasma glucose and HbA1c, respectively. In the replication sample, cg19690313 in TXNIP was associated with both fasting plasma glucose (P = 1.23 × 10-17, FDR < 0.001) and HbA1c (P = 2.29 × 10-18, FDR < 0.001). Furthermore, cg04816311, cg08309687, and cg09249494 may provide new insight in the metabolic mechanism of HbA1c. Our study provides solid evidence that cg19690313 on TXNIP correlates with HbA1c and fasting plasma glucose levels.