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Genome-wide DNA methylation analysis in schizophrenia with tardive dyskinesia: a preliminary study.

Authors
  • Zhang, Ping1
  • Lu, Yongke2
  • Li, Yanli1
  • Wang, Kesheng3
  • An, Huimei1
  • Tan, Yunlong4
  • 1 Beijing HuiLongGuan Hospital, Peking University HuiLongGuan Clinical Medical School, Beijing, 100096, China. , (China)
  • 2 Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, 25755, USA.
  • 3 Department of Family and Community Health, School of Nursing, Health Sciences Center, West Virginia University, Office 6419, Post Office Box 9600, Morgantown, WV, 26506, USA. [email protected].
  • 4 Beijing HuiLongGuan Hospital, Peking University HuiLongGuan Clinical Medical School, Beijing, 100096, China. [email protected]. , (China)
Type
Published Article
Journal
Genes & genomics
Publication Date
Oct 01, 2023
Volume
45
Issue
10
Pages
1317–1328
Identifiers
DOI: 10.1007/s13258-023-01414-5
PMID: 37414911
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Tardive dyskinesia (TD) develops in 20-30% of schizophrenia patients and up to 50% in patients > 50 years old. DNA methylation may play an important role in the development of TD. DNA methylation analyses in schizophrenia with TD. We conducted a genome-wide DNA methylation analysis in schizophrenia with TD using methylated DNA immunoprecipitation coupled with next-generation sequencing (MeDIP-Seq) in a Chinese sample including five schizophrenia patients with TD and five without TD (NTD), and five healthy controls. The results were expressed as the log2FC, fold change of normalized tags between two groups within the differentially methylated region (DMR). For validation, the pyrosequencing was used to quantify DNA methylation levels of several methylated genes in an independent sample (n = 30). Through genome-wide MeDIP-Seq analysis, we identified 116 genes that were significantly differentially methylated in promotor regions in comparison of TD group with NTD group including 66 hypermethylated genes (top 4 genes are GABRR1, VANGL2, ZNF534, and ZNF746) and 50 hypomethylated genes (top 4 genes are DERL3, GSTA4, KNCN, and LRRK1). Part of these genes (such as DERL3, DLGAP2, GABRR1, KLRG2, LRRK1, VANGL2, and ZP3) were previously reported to be associated with methylation in schizophrenia. Gene Ontology enrichment and KEGG pathway analyses identified several pathways. So far, we have confirmed the methylation of 3 genes (ARMC6, WDR75, and ZP3) in schizophrenia with TD using pyrosequencing. This study identified number of methylated genes and pathways for TD and will provide potential biomarkers for TD and serve as a resource for replication in other populations. © 2023. The Author(s) under exclusive licence to The Genetics Society of Korea.

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