The causal association between Celiac disease and Ankylosing spondylitis: a two-sample Mendelian randomization analysis

Abstract Objective The concept of the gut-joint axis is often mentioned when exploring the pathogenesis of Ankylosing spondylitis (AS). This study aims to explore whether there is a causal association between Celiac disease (CeD) and AS. Method Two-sample Mendelian randomization (MR) analysis was conducted using the CeD dataset (the largest pure CeD phenotype dataset in the IEU OpenGWAS database at the time of data retrieval, n = 24,269) and the AS dataset (strictly defined, from the IEU OpenGWAS database, n = 218,030). Inverse Variance Weighting (IVW) was adopted as the primary MR analysis method, supplemented by Weighted Median Estimator, MR-Egger regression, Simple Mode, and Weighted Mode to comprehensively evaluate the causal association between CeD and AS. Additionally, horizontal pleiotropy, heterogeneity, and leave-one-out analysis were performed to further evaluate the robustness and reliability of the results. Results IVW analysis showed a positive causal effect of genetically predicted CeD on AS (OR: 1.435, 95% CI: 1.210–1.702, p = 3.34E-05), and the other four analytical methods also yielded consistent causal effect evaluation results. No significant horizontal pleiotropy or heterogeneity was observed in this study. Conclusion MR analysis indicates that CeD may be a potential risk factor for AS, providing genetic evidence for the increased risk of AS in individuals with a genetic predisposition to CeD.