Insomnia and risk of sepsis: A Mendelian randomization study

Importance Insomnia has been associated with reduced immune function and increased risk of infections and sepsis in observational studies. These studies are prone to bias, such as residual confounding. To further understand the causal relation between insomnia and sepsis risk we used a two-sample Mendelian randomization (MR) approach. Objective Is genetically predicted insomnia associated with risk of sepsis? Design Two-sample MR was performed to estimate the causal effect of genetically predicted insomnia on sepsis risk. Data was obtained from a genome-wide association study (GWAS) identifying 556 independent genetic variants ( R 2 <0.01) strongly associated with insomnia ( P < 5e-8). We conducted sensitivity analyses to address bias due to pleiotropy and sample overlap, along with mediation analyses. Setting Observational study using genetic variants as instrumental variables in large populations. Participants For insomnia, 2.4 million subjects of European ancestry from the UK Biobank and 23andMe. For sepsis, 462,918 subjects of European ancestry from the UK Biobank. Exposure Genetically predicted insomnia. Main Outcome and Measure Sepsis. Results A doubling in the population prevalence of genetically predicted insomnia was associated with an odds ratio of 1.42 (95% CI 1.23–1.63, P = 9.1e-7) for sepsis. Sensitivity analyses supported this observation. Three quarters of the effect was mediated through body mass index. Conclusions and Relevance The concordance between our findings and previous observational studies support of a causal role of genetically predicted insomnia in the risk of sepsis.