The causal relationship between cathepsins and ankylosing spondylitis: a two-sample Mendelian randomization study.

Background: Cathepsins are pivotal regulators of critical physiological processes implicated in cancer, rheumatic disorders, and inflammatory conditions. Objectives: This study employed Mendelian randomization (MR) to evaluate causal relationships between cathepsins and ankylosing spondylitis (AS). Design: A retrospective study. Methods: Single nucleotide polymorphism data of cathepsins were obtained from the INTERVAL study, and AS data were obtained from the FinnGen database. Inverse variance weighting was used as the primary method to assess the causal relationship described above. Cochran's Q test, MR Egger intercept test, MR-PRESSO, and leave-one-out method were used to analyze study sensitivity, heterogeneity, and pleiotropy. Results: In the forward MR analysis, inverse variance weighted results indicated that higher cathepsin S might be associated with an increased risk of AS (inverse-variance weighting, odds ratio = 1.08, 95% confidence interval = 1.00-1.16, p = 0.047). MR-Egger intercept test and Cochran's Q test did not detect significant heterogeneity or horizontal pleiotropy of instrumental variables. The leave-one-out method confirmed the reliability of causality. The reverse MR analysis found no significant causal relationship between cathepsins and AS. Conclusion: Our MR analysis results suggest a potential causal relationship between cathepsin S and AS. Further studies on the pathogenesis of cathepsin-mediated AS may provide new insights into the prevention and treatment of AS.