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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used only openly available human data that were originally located at: UK biobank and 23andMe. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced are available online at