Insomnia, recognized as a prevalent sleep disorder, has garnered extensive attention within the realm of public health. Recent studies indicate a close interaction between the immune system and sleep; however, the specific mechanism remains not yet fully understood. Based on the publicly available Genome-Wide Association Study (GWAS) data, we used two-sample Mendelian randomization (MR) analyses to investigate the associations between 731 immune cell traits and insomnia risk. Five MR analysis methods and a comprehensive sensitivity analysis were used to evaluate the reliability of the results. In this study, we identified that 14 immune characteristics among four immune profiles [median fluorescence intensity (MFI), relative cell count (RC), absolute cell count (AC), and morphological parameters (MP)] demonstrated a significant causal association with insomnia. Specifically, eight immune cell characteristics were associated with an increased risk of insomnia, including CD11c+ monocyte% (P < 0.001), CD11c+ HLA DR++ monocyte% (P = 0.004), CD86+ plasmoid dendritic cell (DC) AC (P < 0.001), CD33br HLA DR+ CD14dim AC (P < 0.001), CD8dim AC (P = 0.002), CCR2 on CD14+ CD16- monocyte (P < 0.001), CD39 on monocyte (P < 0.001), and SSC-A on myeloid DC (P < 0.001). Six immune cell characteristics demonstrated protective effects against insomnia, including PB/PC %B cell (P < 0.001), CM CD4+% CD4+ (P < 0.001), T-cell AC (P < 0.001), BAFF-R on IgD- CD38br (P < 0.001), CD16-CD56 on HLA DR+ NK cells (P < 0.001), and CD14 on CD33br HLA DR+ CD14dim (P < 0.001). Our study established the correlation between immune cell characteristics and insomnia, offering a novel theoretical foundation for the concept of sleep-immune cross talk.NEW & NOTEWORTHY This study investigated the association between 731 immune cell characteristics and insomnia using Mendelian randomization, revealing that 14 immune cell characteristics across four groups of immune traits (MFI, RC, AC, and MP) have a significant and causal association with insomnia risk. Our results contribute to the understanding of the sleep-immune cross talk doctrine and offer a new theoretical basis for immune modulation in treating insomnia.
Keywords: Mendelian randomization; correlation; immune cell characteristics; insomnia.