Association Between 10 Autoimmune Diseases and Risk of Pulmonary Tuberculosis: A Mendelian Randomization Study

Area of Science:

• Genetics
• Immunology
• Epidemiology

Background:

• Pulmonary tuberculosis (PTB) may involve autoimmune processes, but the underlying causes remain unclear.
• Investigating the genetic links between autoimmune diseases and PTB is crucial for understanding disease etiology.

Purpose of the Study:

• To determine the causal genetic relationships between liability to autoimmune diseases (AIDs) and PTB using Mendelian randomization (MR).
• To identify specific autoimmune conditions that may influence the risk of developing PTB.

Main Methods:

• Utilized genome-wide association study (GWAS) datasets to identify single nucleotide polymorphisms (SNPs) for 10 AIDs and PTB.
• Employed three MR approaches (IVW, weighted median, MR-Egger) to assess causal associations.
• Conducted sensitivity analyses to evaluate result robustness, including heterogeneity and pleiotropy assessments.

Main Results:

• No significant causal genetic links were found between seven AIDs (RA, asthma, CD, SLE, PsO, MS, AS) and PTB.
• Inflammatory bowel disease (IBD), celiac disease (CeD), and primary sclerosing cholangitis (PSC) were significantly associated with a decreased risk of PTB.
• Sensitivity analyses confirmed the reliability of these findings.

Conclusions:

• Genetically predicted IBD, CeD, and PSC may act as protective factors against PTB.
• The absence of a causal link between other AIDs and PTB suggests unmeasured confounders or shared genetic factors may explain observed associations.
• This MR study provides insights into the complex interplay between autoimmune diseases and tuberculosis susceptibility.