背景:作为最常见的睡眠障碍,慢性失眠症(CID)已成为全球公众的健康负担。然而,目前尚不清楚这种疾病的发病机制。表观遗传变化可能为CID中的基因-环境相互作用提供重要见解。因此,本研究旨在探讨CID的DNA甲基化模式,揭示该病的表观遗传机制。
方法:在本研究中,从8CID患者(CID组)和8名健康对照者(对照组)中提取全血DNA,分别。此外,通过Illumina人类甲基化850KBeadchip检测到全基因组DNA甲基化。此外,通过匹兹堡睡眠质量指数(PSQI)和失眠严重程度指数(ISI)评估睡眠质量和失眠严重程度,分别。
结果:在CID组和对照组之间共鉴定出369个差异甲基化位置(DMPs)和23个差异甲基化区域(DMRs)。LHX6被鉴定为最重要的差异甲基化基因(DMG)。基因本体论(GO)分析结果证实,DMPs在105个GO术语中显著富集,包括细胞信号,质膜粘附分子的均质细胞粘附,神经系统发育,细胞粘附,和钙离子结合。此外,研究表明,DMP在京都基因和基因组百科全书(KEGG)途径中显著丰富,包括河马信号通路,Ras信号通路,和维生素B6代谢。DMR相关的GO分析结果揭示了蛋白激酶活性的正调节。
结论:DNA甲基化在CID的发展中起关键作用,LHX6被验证为重要的DMG。
BACKGROUND: As the most common sleep disorder, chronic insomnia disorder (CID) has become a global health burden to the public. However, it remains unclear about the pathogenesis of this disease. Epigenetic changes may provide important insights into the gene-environment interaction in CID. Therefore, this study was conducted to investigate the DNA methylation pattern in CID and reveal the epigenetic mechanism of this disease.
METHODS: In this study, whole blood DNA was extracted from 8 CID patients (the CID group) and 8 healthy controls (the control group), respectively. Besides, genome-wide DNA methylation was detected by Illumina Human Methylation 850 K Beadchip. Moreover, the sleep quality and insomnia severity were evaluated by the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI), respectively.
RESULTS: A total of 369 differentially methylated positions (DMPs) and 23 differentially methylated regions (DMRs) were identified between the CID and control groups.
LHX6 was identified as the most important differentially methylated gene (DMG). The Gene Ontology (GO) analysis results corroborated that DMPs were significantly enriched in 105 GO terms, including cell signaling, homogenous cell adhesion of plasma membrane adhesion molecules, nervous system development, cell adhesion, and calcium ion binding. In addition, it was demonstrated that DMPs were significantly enriched in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including the hippo signaling pathway, Ras signaling pathway, and vitamin B6 metabolism. The DMR-related GO analysis results revealed the positive regulation of protein kinase activities.
CONCLUSIONS: DNA methylation plays a critical role in the development of CID, and
LHX6 is validated to be an important DMG.