Causal relationship between rheumatoid arthritis and bronchiectasis: a bidirectional mendelian randomization study.

Area of Science:

• Genetics
• Epidemiology
• Respiratory Medicine

Background:

• Observational studies suggest a link between rheumatoid arthritis (RA) and bronchiectasis.
• The causal relationship between RA and bronchiectasis remains unclear.
• Mendelian randomization (MR) is a robust method to investigate causality.

Purpose of the Study:

• To investigate the bidirectional causal relationship between rheumatoid arthritis and bronchiectasis using a two-sample MR analysis.
• To clarify whether genetic predisposition to RA increases the risk of bronchiectasis.
• To determine if bronchiectasis genetically influences the risk of developing RA.

Main Methods:

• Utilized summary statistics for RA and bronchiectasis from the IEU OpenGWAS database.
• Employed various MR methods including Inverse Variance Weighting (IVW), MR-Egger, and weighted median.
• Conducted sensitivity analyses (Cochran's Q test, MR-Egger intercept, leave-one-out) to ensure analytical robustness.

Main Results:

• A genetic predisposition to RA was significantly associated with an increased risk of bronchiectasis in European and East Asian populations (IVW OR: 1.28 and 1.55, respectively).
• Results were consistent across multiple MR methods.
• No evidence of horizontal pleiotropy or heterogeneity was detected in sensitivity analyses.
• Reverse MR analysis showed no significant causal effect of bronchiectasis on RA risk.

Conclusions:

• Genetic predisposition to rheumatoid arthritis is a risk factor for developing bronchiectasis.
• These findings support screening RA patients for bronchiectasis.
• Effective RA management may potentially reduce bronchiectasis risk.