The Causal Relationship Between Autoimmune Diseases and Sepsis:A Two-Sample Bidirectional Mendelian Randomization Study

Abstract

Abstract Objectives The aim of this Mendelian randomization (MR) study was to assess the potential association between liability to autoimmune diseases (ADs) and the risk of sepsis. Methods Data on autoimmune diseases, including ankylosing spondylitis (AS) (n = 273,824), rheumatoid arthritis (RA) (n = 253,417), sicca syndrome (SS) (n = 368,028), and systemic lupus erythematosus (SLE) (n = 12,730,023), were obtained from the FinnGen database. Data on sepsis (n = 12,730,023) were obtained from the UK Biobank genome-wide association study pooled data. Bi-directional MR analysis was conducted to explore potential causal relationships. The primary analysis employed the inverse variance-weighted (IVW) method to estimate causal effects, with MR-Egger, weighted median, simple mode, and weighted mode as supplementary methods. Sensitivity analyses, including Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis, were performed to assess the robustness of the results. Result The forward MR analysis results indicated that SS (IVW: OR = 1.07, 95% CI: 1.02–1.12, p = 0.01) and SLE (IVW: OR = 1.05, 95% CI: 1.01–1.09, p = 0.01) might be associated with increased risk of sepsis, whereas the AS and RA were no association with sepsis. Reversed MR showed no effect of sepsis on four autoimmune diseases. Conclusions Our findings suggest a potential relationship between SS and SLE and an increased risk of sepsis. These results lay the groundwork for future clinical investigations into the causal association between SS, SLE, and sepsis.