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

• Published in: Genes & genomics 2023, 45(10), , pp.1317-1328
• Main Authors: Zhang, Ping, Lu, Yongke, Li, Yanli, Wang, Kesheng, An, Huimei, Tan, Yunlong
• Format: Article
• Language: English
• Subjects: Analysis; Animal Genetics and Genomics; biomarkers; Biomedical and Life Sciences; DNA; DNA methylation; Dyskinesia; gene ontology; Genes; Genetic research; Genomes; Genomics; high-throughput nucleotide sequencing; Human Genetics; Immunoprecipitation; Life Sciences; Mental disorders; Methylation; Microbial Genetics and Genomics; Movement disorders; Next-generation sequencing; Plant Genetics and Genomics; precipitin tests; Research Article; Schizophrenia; Tardive dyskinesia; 생물학
• ISSN: 1976-9571; 2092-9293; 2092-9293
• DOI: 10.1007/s13258-023-01414-5

Background 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. Objective DNA methylation analyses in schizophrenia with TD. Methods 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 log 2 FC, 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). Results 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. Conclusions 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.