Causal associations between severe mental illness and sepsis: a Mendelian randomization study

SMI (severe mental illness) has been identified as a risk factor for sepsis in observational studies; however, the causal association between them has yet to be firmly established. We conducted MR (mendelian randomization) to unveil the causal relationship between SMI and sepsis as well as sepsis mortality.GWAS (Genome-wide association) data for major depression and schizophrenia were selected as exposure. GWAS data for sepsis and sepsis mortality were selected as outcome. Genetic variants significantly associated with the exposure (P value<1x10-6) were selected as instruments. We primarily employed the IVW (inverse-variance weighted) method for analysis. Furthermore, we employed Cochrane's Q test to assess heterogeneity and the MR-Egger intercept test to identify horizontal pleiotropy.We selected 108 SNPs (single nucleotide polymorphism) used to predict major depression and 260 SNPs that predicted schizophrenia. Genetically predicted major depression was suggestively linked to a higher sepsis risk (OR=1.13, 95%CI 1.02-1.26, P=0.023). In contrast, MR analysis did not find an association between schizophrenia and sepsis risk (OR=1.00, 95%CI 0.97-1.04, P=0.811). Furthermore, no significant causal evidence was found for genetically predicted SMI in sepsis mortality. Moreover, no heterogeneity and horizontal pleiotropy were detected.Our research revealed a suggestive association between genetically predicted major depression and an elevated risk of sepsis in individuals of European ancestry. This finding can serve as a reminder for clinicians to consider the possibility of subsequent infection and sepsis in depressive patients, which may help reduce the incidence of sepsis in individuals with depression.