This study conducted a genome-wide DNA methylation analysis on Chinese Han patients with Chronic Insomnia Disorder (CID), with the main goal of exploring its potential epigenetic mechanisms. The research team extracted whole blood DNA from 8 CID patients and 8 healthy controls, and performed methylation profiling using the Illumina Human Methylation 850K BeadChip. At the same time, participants' sleep quality and insomnia severity were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI), respectively.

The results revealed 369 significantly differentially methylated positions (DMPs) and 23 differentially methylated regions (DMRs) between the CID and control groups. Among these, the LHX6 gene was identified as the most representative differentially methylated gene. Further gene function analysis showed that these DMPs were involved in several important biological processes, including cell signaling, nervous system development, cell adhesion, and calcium ion binding. KEGG pathway analysis indicated that the observed changes were associated with the Hippo signaling pathway, Ras signaling pathway, and vitamin B6 metabolism. In addition, the DMRs were linked to the upregulation of protein kinase activity.

Conclusion: This study confirms that DNA methylation plays a critical role in the pathogenesis of CID. The LHX6 gene may serve as an important epigenetic marker for insomnia, offering new insights into the molecular mechanisms of CID and potential directions for future treatment strategies.

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 insomnia disorder." Sleep and Breathing 28.6 (2024): 2397-2407.

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