The opposite patterns of DNA methylation between female and male children from tic disorders by a case-control study

Abstract

Tic disorders can affect the quality of life in both childhood and adolescence. Many factors are involved in the etiology of tic disorders, and the genetic and epigenetic factors of tic disorders are considered complex and heterogeneous. In this study, the differentially methylated regions (DMRs) between normal controls (n = 24; aged 6–15; 7 females) and patients with tic disorders (n = 16; aged 6–15; 5 females) were analyzed. We performed an epigenome-wide association study (EWAS) of tic disorders in Korean children. The severity of the tics was measured using a self-report version of the YGTSS. The DNA methylation data consisted of 726,945 CpG sites, assessed using the Illumina Infinium MethylationEPIC (850k) BeadChip. The DNA methylation data of the 40 participants were retrieved, and DMRs between the four groups based on sex and tic disorder were identified. From 28 male and 16 female samples, 37 and 38 DMRs were identified, respectively. We analyzed the enriched terms and visualized the network, heatmap, and upset plot. In male, KEGG enrichment analysis revealed hypomethylated patterns in the ligand, receptor, and second signal transductors of the MAPK, Ras, Rap1, and PI3K-Akt signaling pathway, and in female, the opposite patterns were revealed. Five mental disorder-related enriched terms were identified in the network analysis. Here, we provide insights into the epigenetic mechanisms of tic disorders. Abnormal DNA methylation patterns are associated with mental disorder-related symptoms.