EP300 Regulates CD8br AC (TBNK Panel) to Facilitate Insomnia.

Insomnia is a prevalent clinical condition that is caused by the interaction of environmental, inflammatory, immune system, physiological, and psychological factors. Nevertheless, the significance of lactylation-related gene in the pathogenesis of insomnia remains unknown. The causal relationship between lactylation-related gene and insomnia was initially analyzed using Mendelian randomization. Exposure was determined using cis-expression quantitative trait loci (cis-eQTL) from the Expression Quantitative Trait Locus Gen (eQTLGen) consortium. We obtained insomnia from the FinnGen database, which comprises 490,763 controls and 6776 cases. Subsequently, we performed a difference analysis of the Gene Expression Omnibus (Geo) data on insomnia and a summary-data-based MR (SMR) analysis to further validate our findings. We used a mediation approach by immune cells to study the effect of lactylation-related genes on insomnia. We identified one lactylation-related gene associated with insomnia. EP300 also passed the SMR test (p < 0.05), and heterogeneity was assessed using the auxiliary heterogeneity in dependent instruments (HEIDI) test (p > 0.05). Using data from the Geo database, the overall difference in EP300 expression between insomnia patients and healthy individuals was compared and found to be significant. A mediation analysis was employed to investigate the impact of immune cells and EP300 on insomnia. We found that EP300 may promote insomnia by regulating the CD8br AC (TBNK panel). This provides new insights into the relationship between lactylation-related genes and insomnia and serves as a novel therapeutic target for future research.