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从基因层面揭示户外活动与近视的因果关系:基于孟德尔随机化原理OA

Revealing the causal relationship between outdoor activities and myopia from genetic level:based on Mendelian randomization

中文摘要英文摘要

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.

魏熙翔;杨晖

厦门市儿童医院,复旦大学附属儿科医院厦门医院,厦门 361006

临床医学

因果关系孟德尔随机化户外活动近视

causal relationshipMendelian randomizationoutdoorsmyopia

《眼科学报》 2024 (005)

246-258 / 13

厦门市医疗卫生项目(指导性项目)(3502Z20214ZD1240);厦门市医工结合指导性项目(3502Z20244ZD2058).This work was supported by Medical and Health Project of Xiamen Guidance Project(3502Z20214ZD1240)and Xiamen Medical and Engineering Integration Guidance Project(3502Z20244ZD2058).

10.12419/24053101

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