ASSESSING THE CAUSAL RELATIONSHIP BETWEEN SEPSIS AND AUTOIMMUNE: A MENDELIAN RANDOMIZATION STUDY.

Objective : Numerous epidemiological studies have identified a potential link between sepsis and a variety of autoimmune disorders. The primary objective of this study is to delve deeper into this connection, investigating the potential causal relationship between sepsis and autoimmune disorders through the application of Mendelian randomization (MR). Methods : To assess the potential genetic impact on sepsis risk relating to susceptibility toward immune-related outcomes, we used summary data from the largest European genome-wide association studies (GWAS) on these conditions using a two-sample MR framework. Single nucleotide polymorphisms-which had strong associations with the nine traits-were extracted from the GWAS and examined their effects in an extensive European sepsis GWAS (486,484 cases and 474,841 controls). We used inverse-variance weighted MR, weighted median, and MR Egger for analyses, supplementing these with sensitivity analyses and assessing level pleiotropy using MR methodologies. We also executed a reverse MR analysis to test sepsis' causal effects on the designated autoimmune traits. Results : With primary sclerosing cholangitis being the exception, our MR analysis suggests that susceptibility toward most autoimmune diseases does not affect sepsis risks. The reverse MR analysis did not validate any influence of sepsis susceptibility over other autoimmune diseases. Our primary inverse-variance weighted MR analysis outcomes found general confirmation through our sensitivity MR examinations. Variance in the exposures, as dictated by the single nucleotide polymorphism sets used as MR instruments, ranged between 4.88 × 10 -5 to 0.005. Conclusion : Our MR research, centered on a European population, does not validate a correlation between susceptibility to the majority of autoimmune disorders and sepsis risk. Associations discerned in epidemiological studies may owe partly to shared biological or environmental confounders. The risk susceptibility for primary sclerosing cholangitis does relate to sepsis risk, opening doors for personalized precision treatments in the future.