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Updated: Jul 19, 2025

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Association of Genetically Predicted Insomnia With Risk of Sepsis: A Mendelian Randomization Study

Marianne S Thorkildsen1, Lise T Gustad1,2,3, Randi M Mohus1,4

  • 1Gemini Center for Sepsis Research at Institute of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.

JAMA Psychiatry
|August 9, 2023
PubMed
Abstract

Insights

Insomnia is causally linked to an increased risk of sepsis. This sleep disorder may be a preventable factor for sepsis, particularly in women.

Area of Science:

  • Genetics
  • Epidemiology
  • Sleep Medicine

Background:

  • Observational studies suggest a link between insomnia, inflammation, and sepsis risk.
  • These studies are limited by potential biases like residual confounding.
  • A Mendelian randomization approach is needed to explore a causal association.

Purpose of the Study:

  • To investigate the potential causal relationship between genetically predicted insomnia and the risk of developing sepsis.
  • To assess if insomnia is an independent risk factor for sepsis.

Main Methods:

  • A two-sample Mendelian randomization (MR) study was conducted.
  • Genetic variants strongly associated with insomnia were identified from large-scale genome-wide association studies (GWAS) of European ancestry.
  • Sepsis data was obtained from the UK Biobank, with sensitivity and mediation analyses performed.

Main Results:

  • A doubling in genetically predicted insomnia prevalence was associated with a 37% increased odds of sepsis (OR, 1.37; 95% CI, 1.19-1.57).
  • Cardiometabolic factors partially mediated this association (35.2%).
  • The insomnia-sepsis link was stronger in women (OR, 1.44) than in men (OR, 1.10).

Conclusions:

  • Findings support a potential causal role of insomnia in sepsis risk.
  • Insomnia may represent a modifiable risk factor for sepsis.
  • Further research, including in diverse populations, is warranted.

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