Effects of insomnia and hypothyroidism on sepsis: a mediated Mendelian randomization analysis

Background. Insomnia and sepsis are both increasingly prevalent conditions, and previous studies have reported an association between them. Moreover, hypothyroidism appears to influence both disorders. This study aimed to further investigate the causal link between insomnia and sepsis, and to examine whether hypothyroidism acts as a mediator in this relationship, offering a reference point for clinical intervention.Methods.We applied multiple Mendelian randomization approaches to explore the causal association between insomnia and sepsis. Initially, a two-sample Mendelian randomization (UVMR) analysis was conducted to assess their direct relationship. Subsequently, multivariable Mendelian randomization (MVMR) was used to evaluate whether hypothyroidism mediates the insomnia–sepsis pathway. To ensure the robustness of the findings, we used several statistical methods including inverse variance weighting (IVW), the weighted median, and MR-PRESSO. We further assessed heterogeneity and horizontal pleiotropy through the MR-Egger intercept, Cochran's Q test, and leave-one-out analysis.Results.MR analysis indicated that insomnia increased the risk of sepsis (IVW: OR = 1.485, 95% CI [1.090–2.023]). Mediation analysis showed that hypothyroidism accounted for 5.57% (3.93%–7.20%) of the effect of insomnia on sepsis.Conclusion.These findings indicate a causal relationship between insomnia and sepsis, with hypothyroidism partially mediating this link. Addressing hypothyroidism may reduce the risk of sepsis in individuals suffering from insomnia.