Genetic links between psychological distress, sleep disorders, and sepsis risk: a Mendelian randomization study.

Background: Psychological distress and sleep disorders have been associated with increased sepsis risk and mortality, but their causal genetic relationships remain unclear.

Aim: This study aimed to evaluate the causal relationship between genetically predicted psychological distress, sleep disorders, and sepsis risk, using a two-sample Mendelian randomization approach.

Method: Genetic instrumental variables were identified for anxiety disorders, depression, post-traumatic stress disorders (PTSD), insomnia, and sleep-wake schedule disorders. Genome-wide association study (GWAS) data were used as exposure datasets, and five sepsis severity levels were analyzed. The inverse-variance weighted (IVW) method was the primary analysis, supported by the MR-Egger and weighted median methods. Heterogeneity was assessed using Cochran's Q test and pleiotropy was evaluated using the MR-Egger intercept test. A Leave-one-out sensitivity analysis was conducted to ensure robustness.

Results: MR analysis found that genetically predicted depression was significantly associated with increased sepsis risk in individuals under 75 years of age (OR 1.15, 95% CI 1.03-1.28; P = 0.016), while PTSD was associated with a higher likelihood of requiring critical care for sepsis (OR 1.11, 95% CI 1.04-1.18; P = 0.002). No significant associations were found between other psychological distress factors, sleep disorders, and the risk of sepsis. Sensitivity analyses confirmed the stability of these results.

Conclusion: This study provides genetic evidence linking depression and PTSD to sepsis risk and severity, emphasizing the need for clinical awareness and targeted interventions in at-risk individuals.