The role of lipid metabolism and immune response in the pathogenesis of Ankylosing spondylitis and Primary glaucoma: A Bidirectional Mendelian Randomization Study

Abstract

Background Ankylosing Spondylitis (AS) is known to be associated with secondary glaucoma, largely due to complications of acute anterior uveitis and corticosteroid use. However, the relationship between AS and primary glaucoma is more complex and has yet to be fully elucidated. To investigate this relationship further, we used the Bidirectional Mendelian randomization (MR) analysis to evaluate the potential causal relationship between AS and primary glaucoma, and further elucidate possible pathogenic mechanisms. Methods We estimated the causal effect of ankylosing spondylitis on primary glaucoma using a bidirectional Mendelian randomization approach. In addition to assessing the direct causal link, we also explored the mediation effects of lipid metabolism and immune response. To ensure the robustness of our findings, we supplemented our primary analysis with a series of sensitivity analyses and reverse MR. Results Bidirectional Mendelian randomization suggest that AS is related to an increased risk of primary glaucoma (odds ratio: 1.20, 95% confidence interval:1.03–1.40; P = 0.018). Lipid metabolism including very low-density lipoprotein (VLDL) (P < 0.01, β < 0), and immune response including platelet count (P < 1.0E-06, β > 0), IgD on unswitched memory B cell (P < 1.0E-06, β < 0), and CD8 on CD39 + CD8 + T cell (P < 0.01, β > 0) appear to mediate the ankylosing spondylitis with primary glaucoma. Conclusion Our analysis reveals a significantly increased risk of primary glaucoma in individuals with AS. This heightened risk suggests a complex interaction between AS and primary glaucoma, potentially mediated by factors related to immune response. These findings provide new insights into the pathogenic mechanisms linking these two conditions.