Abstract

Insomnia stands out as a prevalent sleep disorder, with recent research highlighting the significance of psychological factors in its initiation and progression. Nonetheless, the precise biological mechanisms underlying insomnia remain elusive. Although genome-wide association studies have pinpointed numerous genetic loci linked to insomnia, elucidating the underlying biological rationale necessitates further investigation. We utilized the summary data-based Mendelian randomization approach to integrate genomewide association studies with expression quantitative trait loci studies and methylation quantitative trait loci studies. Additionally, we employed the heterogeneity in dependent instruments test to enhance our comprehension of the study findings and to identify and mitigate potential sources of bias or misinterpretation, thereby enhancing the credibility and accuracy of our study. We conducted expression quantitative trait loci analysis using the summary data-based Mendelian randomization method, uncovering 119 loci linked to gene expression. Concurrently, methylation quantitative trait loci analysis identified 491 loci associated with DNA methylation. Encouragingly, nine single nucleotide polymorphisms were found to overlap in both analyses. Subsequently, we conducted additional summary data-based Mendelian randomization analysis on these expression quantitative trait loci and methylation quantitative trait loci data, ultimately revealing 175 mediating models. These models elucidate the regulatory mechanism by which genetic variation influences DNA methylation, thereby modulating gene expression and ultimately influencing insomnia. This discovery offers valuable insights for a more comprehensive understanding of the genetic underpinnings of insomnia.