Epigenome-wide Association Study for Tic Disorders in Children: A Preliminary Study in Korean Population
Young Kyung Ko1,*, Suhyuk Chi2,*, Gyu-Hwi Nam3, Kyung-Wan Baek4, Kung Ahn5, Yongju Ahn5, June Kang6, Moon-Soo Lee2, Jeong-An Gim7
1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea
2Department of Psychiatry, Korea University Guro Hospital, Seoul, Korea
3PhileKorea Technology Co. Ltd., Daejeon, Korea
4Department of Physical Education, Gyeongsang National University, Jinju, Korea
5HuNBiome Co. Ltd., Seoul, Korea
6Department of Brain and Cognitive Engineering, Korea University, Seoul, Korea
7Department of Medical Science, Soonchunhyang University, Asan, Korea
Correspondence to: Moon-Soo Lee
Department of Psychiatry, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 08308, Korea
E-mail: npboard@korea.ac.kr
ORCID: https://orcid.org/0000-0003-0729-6943

Jeong-An Gim
Department of Medical Science, Soonchunhyang University, 22 Soonchunhyang-ro, Sinchang-myeon, Asan 31538, Korea
E-mail: vitastar@sch.ac.kr
ORCID: https://orcid.org/0000-0001-7292-2520

*These authors contributed equally to this work.
Received: June 14, 2023; Revised: September 24, 2023; Accepted: November 24, 2023; Published online: January 10, 2024.
© The Korean College of Neuropsychopharmacology. All rights reserved.

This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Objective: 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.
Methods: 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 of tic disorders in Korean children. The tics were assessed using Yale Global Tic Severity Scale. The DNA methylation data consisted of 726,945 cytosine phosphate guanine (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.
Results: In male, Kyoto Encyclopedia of Genes and Genomes (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.
Conclusion: 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; EWAS; YGTSS.


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