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

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Abstract

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.

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

  • Behavioral Genetics
  • Cardiovascular Genetics
  • Genetic association study
  • Medical Genetics
  • Neonatal sepsis
  • Genetic predisposition to disease

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Acknowledgements

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Funding

This work was supported by Zhejiang Pharmaceutical Association Hospital Pharmacy Special Research Grant Project [NO. 2023ZYY14].

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Author notes

  1. Hui-fang Jiang, Wei Hu and Ting-ting Jin have contributed equally to the work and should be considered co-first authors.

Authors and Affiliations

  1. Department of Pharmacy, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China

    Hui-fang Jiang, Wei Hu, Ting-ting Jin, Hai-li Shan, Tao Zhu, Jun-jun Xu, Yang-min Hu & Hai-bin Dai

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Correspondence to Hai-bin Dai.

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Haibin Dai and Yangmin Hu are corresponding authors and contributed equally to this work.

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Jiang, Hf., Hu, W., Jin, Tt. et al. Genetic links between psychological distress, sleep disorders, and sepsis risk: a Mendelian randomization study. Int J Clin Pharm (2025). https://doi.org/10.1007/s11096-025-01931-1

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  • DOI  https://doi.org/10.1007/s11096-025-01931-1

Keywords

  • Mendelian randomization
  • Psychological distress
  • Sepsis
  • Sleep disorders

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