Methylation differences in 3 pairs of identical twin adolescents with different depressive phenotypes

Abstract

Objective To investigate the differences of peripheral blood DNA methylation in identical twin adolescents with different depressive phenotypes and explore whether these differentially expressed genes can be used as candidate genes involved in the occurrence of depression. Methods Three pairs of verified identical twin adolescents (12~18 years old) were recruited in this study. Phenotypic differences of depression between the twins were determined by Beck Depression Inventory-Ⅱ (BDI-Ⅱ) scores and emotional factor scores of Strength and Difficulty Questionnaire (SDQ) for students. After Infinium MethylationEPIC BeadChip Kit was used to interrogate over 850k methylation sites, those with P 0.1) were selected as the differential methylation sites. Gene Ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, as well as protein-protein interaction (PPI) network were performed to identify important genes associated with major depressive disorder (MDD) and their methylation changes. Results Three pairs of identical twin adolescents with different depressive phenotypes were divided into depressive phenotype group and normal phenotype group. A total of 57 genes with different methylation levels were screened between the 2 groups, including 45 genes with increased and 12 genes with decreased DNA methylation levels. GO analysis showed that differential genes were most significantly enriched in biological processes such as central nervous system development and regulation of RNA metabolic process. KEGG analysis indicated that differential genes were significantly enriched in synaptic long-term depression (LTD), PI3K-Akt signaling pathway and TNF signaling pathway. Besides, direct or indirect interactions between RHOA and several differential methylated genes were found in PPI network. Conclusion Changes in DNA methylation levels of CSF1R, NOS1, AHR and other genes in peripheral blood of identical twins with different depressive phenotypes may regulate gene expression through synaptic long-term depression (LTD), PI3C-Akt and other signaling pathways involved in the occurrence of depression.

Keywords

• dna methylation
• depression
• twins
• adolescents