Causal relationship between ankylosing spondylitis and multiple sclerosis: Evidence from 2-sample Mendelian randomization

Ankylosing spondylitis (AS) and multiple sclerosis (MS) are chronic immune-mediated disorders with overlapping epidemiological and genetic features, but their causal relationship remains unclear. In this study, we performed a 2-sample Mendelian randomization (MR) analysis using large-scale genome-wide association study summary statistics from European populations to investigate whether AS causally influences the risk of MS. Instrumental variables were selected based on stringent significance, independence, and validity criteria. The primary MR analyses, including the inverse variance weighted method, indicated that AS is associated with an increased risk of MS (odds ratio = 2.18, 95% confidence interval: 1.31-3.63, P = .00), and this finding was supported by the MR Egger method. Sensitivity analyses confirmed the robustness of the results. Inverse MR analysis found no evidence for a causal effect of MS on AS. These findings contribute to the understanding of the shared genetic architecture and pathophysiological pathways between AS and MS. Further studies in more diverse populations and with nonlinear models are warranted to validate and extend these findings.