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

Area of Science:

• Genetics
• Immunology
• Epidemiology

Background:

• Epidemiological studies suggest a link between sepsis and autoimmune disorders.
• The causal relationship remains unclear, necessitating further investigation.

Purpose of the Study:

• To investigate the potential causal relationship between sepsis and autoimmune disorders using Mendelian randomization (MR).
• To assess the genetic influence of autoimmune disease susceptibility on sepsis risk.

Main Methods:

• Utilized a two-sample MR framework with large-scale European genome-wide association studies (GWAS) data.
• Employed inverse-variance weighted MR, weighted median, and MR Egger analyses.
• Conducted sensitivity analyses and reverse MR to assess causality and pleiotropy.

Main Results:

• MR analysis indicated that susceptibility to most autoimmune diseases does not significantly impact sepsis risk.
• Reverse MR analysis did not support a causal effect of sepsis on autoimmune diseases.
• Primary sclerosing cholangitis susceptibility was identified as a potential risk factor for sepsis.

Conclusions:

• The study does not validate a widespread causal link between autoimmune disorder susceptibility and sepsis risk in Europeans.
• Observed epidemiological associations may be influenced by shared environmental or biological confounders.
• Primary sclerosing cholangitis presents a specific association with sepsis risk, potentially enabling future personalized treatments.