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

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

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.

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.

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.

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.