目的：利用双向孟德尔随机化方法(mendelian randomization,MR)探索骨关节炎与青光眼的潜在因果关系。方法：使用全基因组关联研究(genome-wide association studies,GWAS)数据，挑选出与骨关节炎和青光眼高度相关的单核苷酸多态性(single nucleotide polymorphism,SNP)作为工具变量。本研究以逆方差加权法(inverse variance weighted,IVW)作为主要的分析手段，以加权中位数法、加权模型法、简单众数法及MR-Egger回归法作为辅助方法，采用F统计量、Cochran Q检验、MR Egger截距测试、留一法(leave one out)及多效性残差和离群值法(mendelian randomization pleiotropy RESidual sum and outliers,MR-PRESSO)进行敏感性分析。本研究采用比值比(odds ratio,OR)作为主要的效应量度指标，以95%置信区间(confidence interval,CI)评估关联强度，探讨骨关节炎与青光眼的双向因果关系。结果：IVW结果表明骨关节炎可增加青光眼的患病风险(95%CI: 1.00~1.20，OR=1.10，P=0.043)，辅助方法的结果显示了相同的因果方向，但无统计学意义。在反向MR分析中，IVW结果表明，青光眼不会增加患骨关节炎的风险(OR=1.02，95%CI: 0.97~1.08)，4种辅助方法均支持IVW结果。所选SNP的F统计量均超过10，无弱工具变量。Cochran Q检验、MR-Egger截距检验以及MR-PRESSO分析结果均未显示所选SNP之间存在异质性或水平多效性。反向MR分析结果显示Cochran Q检验有异质性，但未发现水平多效性。留一法结果显示没有对整体分析结果产生了显著影响的SNP。结论：正向MR分析表明骨关节炎可能会增加患青光眼的风险，二者之间存在正相关。反向MR分析结果表明，青光眼对骨关节炎无因果效应。

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.

目的：运用孟德尔随机化(Mendelian randomization,MR)方法，探索户外活动与近视之间的双向因果关系。方法：来自英国生物银行(UK Biobank)的大型队列研究数据，选择与欧洲血统人群中户外活动与近视相关的相互独立的遗传位点作为IV。户外活动的全基因组关联研究(genome-wide association study, GWAS)数据包含419 314名欧洲人群，而近视的GWAS数据则包含460 536名欧洲人群，其中37 362名近视者和423 174名对照者。通过运用逆方差加权法(inverse variance weighted,IVW)、加权中位数法(weighted median,WM)以及MR Egger法进行MR分析，将比值比作为效应度量指标，深入探讨两者间的双向因果联系。同时，通过MR多态性残差和异常值检测(MR PRESSO)方法剔除SNP异常值，利用MR Egger法以及IVW法的Cochran Q检验对各个单核苷酸多态性(SNP)之间的异质性进行了评估；并且使用MR Egger截距检验SNP的潜在多效性，通过“留一法”敏感性分析检验MR研究是否受单个SNP的影响。结果：IVW分析显示户外活动能显著降低近视的风险(OR = 0.934, 95% CI: 0.922～0.948, P < 0.01)。反向孟德尔随机化分析发现近视者参与户外活动的意愿较低(OR = 0.925, 95%CI: 0.777～1.103)但P = 0.39，未达到统计学意义。双向孟德尔随机化分析的Cochran Q检验、MR PRESSO检测以及MR Egger截距测试结果均显示所选IV间不存在显著异质性和水平多效性问题，而且，“留一法”敏感性分析证实，单个SNP对整体结果未见影响。结论：户外活动可能明显降低近视的风险。

Objective: To employ Mendelian randomization (MR) methods to explore bidirectional causal relationships between outdoor activities and myopia. Methods: Large-scale cohort study data from the UK Biobank were utilized, selecting independent genetic loci associated with outdoor activities and myopia within the European ancestry population as instrumental variables. The outdoor activities GWAS data included 419,314 individuals of European descent, while the myopia GWAS data comprised 460,536 individuals, including 37,362 myopia cases and 423,174 controls. MR analyses were conducted using inverse variance-weighted (IVW), weighted median, and MR Egger methods, employing the odds ratio as the effect measure to thoroughly investigate bidirectional causal connections. Mendelian randomization pleiotropy residual sum and outlier (MR PRESSO) detection method were employed to eliminate SNP outliers. Cochran's Q test, within MR Egger and IVW methods, was utilized to assess heterogeneity among individual single nucleotide polymorphisms (SNPs). MR Egger intercept testing assessed potential pleiotropy, and sensitivity analysis using the "leave-one-out" method examined the influence of individual SNPs on overall results. Results: IVW analysis demonstrated that outdoor activities significantly reduce the risk of myopia (OR = 0.934, 95% CI: 0.922~0.948, P < 0.01). Reverse Mendelian randomization analysis revealed a non-significant lower propensity for myopic individuals to engage in outdoor activities (OR = 0.925, 95% CI: 0.777~1.103, P = 0.39). Cochran's Q test, MR PRESSO, and MR Egger intercept tests in bidirectional Mendelian randomization analysis all indicated no significant heterogeneity or horizontal pleiotropy issues among the selected instrumental variables. Furthermore, sensitivity analysis using the "leave-one-out" method confirmed that individual SNPs did not significantly impact the overall results. Conclusion: Outdoor activities significantly reduce the risk of myopia.