Causal Association Between Ankylosing Spondylitis and Hidradenitis Suppurativa: A Twosample Bidirectional Mendelian Randomization Study

Background: Ankylosing spondylitis (AS) and hidradenitis suppurativa (HS) represent two chronic inflammatory diseases that share similar underlying immunological characteristics. Observational studies suggest a potential association, but the causal relationship remains underexplored. Objective: To evaluate bidirectional causal links between AS and HS using Mendelian randomization (MR). Methods: We implemented two-sample bidirectional MR analyses, utilizing summary statistics obtained from genome-wide association study (GWAS) datasets. Genetic instruments for AS (ncase=9069, ncontrol=1550) and HS (ncases=409, ncontrols=211,139) were selected under stringent criteria (p< 5e-5 LD clumping: r 2 < 1e-2, clumping window=1e4 kb). Primary analyses used inverse-variance weighted (IVW) regression, supplemented by MR-Egger, weighted median, and sensitivity analyses. Results: Genetically predicted AS significantly increased HS risk (IVW OR=3.49, 95% CI=1.43– 8.52, P=0.006), with no evidence of reverse causation (HS→AS: OR=1.00, 95% CI=0.9998– 1.00, P=0.816). To validate the stability of our estimates, sensitivity analyses were performed. The MR-Egger intercept and Cochran’s Q test yielded nonsignificant P values (both P> 0.05), supporting the robustness of our findings. Conclusion: This investigation provides genetic evidence indicating a causal relationship between ankylosing spondylitis and an increased risk of hidradenitis suppurativa, underscoring a shared etiological pathway, likely involving the IL-17/IL-23 axis. No significant causal effect was observed from HS to AS within the limitations of the current data. Keywords: ankylosing spondylitis, hidradenitis suppurativa, Mendelian randomization study