Causal relationship between rheumatoid arthritis and ankylosing spondylitis: Two-sample Mendelian randomization

Area of Science:

• Rheumatology
• Genetics
• Epidemiology

Background:

• Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are distinct inflammatory arthropathies.
• Understanding their etiological relationship is crucial for effective management.

Purpose of the Study:

• To investigate the potential causal relationship between rheumatoid arthritis and ankylosing spondylitis.
• To leverage genetic data for causal inference.

Main Methods:

• Mendelian randomization (MR) analysis using genetic variants associated with RA and AS in European populations.
• Employed MR-Egger, weighted median, and inverse variance weighting methods.
• Conducted heterogeneity, pleiotropy, and sensitivity analyses (leave-one-out).

Main Results:

• Inverse variance weighting indicated a significant causal effect of RA on ankylosing spondylitis (OR: 1.25, 95% CI: 1.11-1.41, P < .001).
• No significant heterogeneity or pleiotropy was detected.
• Sensitivity analyses confirmed the robustness of the findings.

Conclusions:

• This study provides strong evidence for a causal relationship where rheumatoid arthritis increases the risk of developing ankylosing spondylitis.
• Genetic insights support a unidirectional causal link from RA to AS.