骨关节炎和青光眼的双向孟德尔随机化研究OA

Objective:To investigate the potential bidirectional causal association between osteoarthritis and glaucoma through the application of bidirectional Mendelian randomization(MR).Methods:Instrumental variables were selected in this study based on single nucleotide polymorphisms(SNP)strongly associated with osteoarthritis and glaucoma,as utilizing genome-wide association studies(GWAS)data.The inverse variance weighting(IVW)method was served as the primary analytical approach,while the weighted median mode,simple plurality and MR-Egger regression methods were employed as complementary methods.Sensitivity analyses were conducted using F-statistic,Cochran Q-test,MR Egger's intercept test,leave-one-out,and multiplicity of residuals and outliers method(MR-PRESSO).The ratio of odds ratios(OR)was adopted as the primary effect estimate,and the strength of association was evaluated by 95%confidence interval(CI)to explore the bidirectional causal relationship between osteoarthritis and glaucoma.Results:The IVW analysis revealed that osteoarthritis elevates the risk of glaucoma with an odds ratio of(OR)of 1.10(95%CI:1.00-1.20).While the adjunctive methods concurred with this causal direction,their findings did not reach statistical significance.In contrast,the inverse Mendelian randomization(MR)analysis utilizing the inverse variance weighting method demonstrated that glaucoma does not enhance the risk of developing osteoarthritis(OR=1.02,95%CI:0.97-1.08).This conclusion was upheld by all four auxiliary methods.The F-statistic values for the selected SNP exceeded 10,indicating the absence of weak instrumental variables.Furthermore,the Cochran Q test,MR-Egger intercept test,and MR-PRESSO analyses revealed no evidence of heterogeneity or horizontal pleiotropy among the SNP.However,the inverse MR analysis displayed heterogeneity in the Cochran Q test,yet no horizontal pleiotropy was detected.The leave-one-out method analysis identified no significant influence of any individual SNP on the overall results.Conclusions:Forward MR analyses indicated that osteoarthritis may serve as a risk factor for glaucoma,indicating a positive correlation between the two conditions.Conversely,reverse MR analysis failed to establish a causal link between glaucoma and osteoarthritis.