Epigenome-wide association study for tic disorders in children: a preliminary study in Korean population
Young Kyung Ko 1, Suhyuk Chi 2, Gyu-Hwi Nam 3, Kyung-Wan Baek 4, Kung Ahn 5, Yongju Ahn 5, June Kang 6, Moon-Soo Lee 2, Jeong-An Gim 7*
1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul 08308, Korea, 2Department of Psychiatry, Korea University Guro hospital, Seoul 08308, Korea, 3PhileKorea Technology Co. Ltd., Daejeon 34025, Korea, 4Department of Physical Education, Gyeongsang National University, Jinju 52828, Korea, 5HuNBiome Co. Ltd., Seoul 08506, Korea, 6Department of Brain and Cognitive Engineering, Korea University, Seoul 02841, Korea, 7Department of Medical Science, Soonchunhyang University, Asan, 31538, Korea
Received: May 31, 2023; Revised: October 23, 2023; Accepted: November 2, 2023; Published online: November 2, 2023.
© The Korean College of Neuropsychopharmacology. All rights reserved.

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 tics were assessed using Yale Global Tic Severity Scale (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 PI3K-Akt and MAPK signaling pathway (most cells were indicated as green color), and in female, the opposite patterns were revealed (most cells were indicated as red color). 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.
Keywords: Tic disorder, DNA methylation, Epigenome-wide association study, Yale Global Tic Severity Scale

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