目的:关于大气污染物是否与年龄相关性白内障有关联的研究有限,以往的研究结果也不一致。本研究旨在评估多种大气污染物与年龄相关性白内障之间的关系。方法:采用双样本孟德尔随机化(Mendelian Randomization, MR)设计,并使用了来自亚洲及欧洲两个人群的独立全基因组关联研究(Genome-Wide Association Study, GWAS)的汇总统计数据。大气污染物数据包括颗粒物2.5(particulate matter2.5, PM2.5)、PM2.5-10、PM10、二氧化氮和氮氧化物。主要分析方法是逆方差加权(inverse variance Weighted, IVW)法,辅以多变量孟德尔随机化分析(multivariable Mendelian randomization, MVMR)校正污染物间混杂效应,并通过敏感性分析验证结果的稳健性。Cochran Q检验法被用来评估各个单核苷酸多态性(single nucleotide polymorphism, SNP)之间是否存在显著的异质性。并采用MR PRESSO方法来识别并排除SNP中的异常值,同时利用MR Egger回归模型评估SNP之间可能存在的多效性,并通过逐一排除每个SNP进行敏感性分析,以确保MR分析结果不受单一SNP的显著影响。结果:关于5种大气污染物特征,亚洲人群结果中,二氧化氮暴露与年龄相关性白内障存在正相关(OR=1.03, 95%CI 1.00~1.06,P=0.026),但在多变量分析中效应方向反转(OR=0.86, 95%CI 0.77~0.97, P=0.013);在欧洲人群中,PM2.5-10与年龄相关性白内障显著相关(OR=1.35, 95%CI 1.12~1.62,P=0.002),且在多变量分析中因果效应依然显著(OR=1.58, 95%CI 1.27~3.70, P=0.03)。敏感性分析支持结果的稳健性,未发现异质性或多效性偏倚。结论:环境中PM2.5-10和二氧化氮与年龄相关性白内障存在复杂因果关系,且因人群而异。亚洲人群中,二氧化氮单变量分析呈正相关,多变量分析效应反转,倾向多变量分析结果,即其降低年龄相关性白内障风险;欧洲人群中,PM2.5-10单、多变量分析均呈正相关,显示其会增加年龄相关性白内障风险。
Objective: Research exploring the association between atmospheric pollutants and age-related cataracts is scarce, and previous studies have yielded inconsistent findings. This study aims to assess the relationship between various atmospheric pollutants and age-related cataracts. Methods: We adopted a two-sample Mendelian randomization (MR) design, using summary statistics from independent genome-wide association studies (GWAS) conducted on Asian and European populations. The atmospheric pollutant considered in this study included PM2.5, PM2.5-10, PM10, nitrogen dioxide, and nitrogen oxides. The primary analysis method was the inverse variance weighted (IVW) approach. Additionally, multivariable MR (MVMR) was used to adjust for confounding effects among pollutants. Sensitivity analyses were conducted to verify the robustness of the results. The Cochran Q test was employed to assess significant heterogeneity among SNPs. The MR PRESSO method was applied to identify and exclude outliers SNPs, while the MR Egger regression model was used to evaluate potential pleiotropy among SNPs. Furthermore, sensitivity analyses were performed by excluding each SNP one by one to ensure that the MR analysis results were not significantly influenced by a single SNP. Results: Among the five atmospheric pollutants studied, we discovered a significant positive correlation between nitrogen dioxide exposure and age-related cataracts in the Asian population (OR=1.03, 95%CI 1.00-1.06, P=0.026). However, the direction of the effect was reversed in the multivariable analysis (OR=0.86, 95%CI 0.77-0.97, P=0.013). In the European population, PM2.5-10 was significantly associated with age-related cataracts (OR=1.35, 95%CI 1.12-1.62, P=0.002), and the causal effect remained significant in the multivariable analysis (OR=1.58, 95%CI 1.27-3.70, P=0.03). Sensitivity analyses supported the robustness of the results, with no evidence of heterogeneity or pleiotropy bias. Conclusions: This study revealed a complex causal relationship between environmental PM2.5-10 and NO₂ and age-related cataracts, which varied across populations. In Asian populations, the univariate analysis of nitrogen dioxide showed a positive correlation, but the effect was reversed in multivariate analysis, leaning towards the multivariate results and indicating a reduced risk of age-related cataracts. In European populations, both univariate and multivariate analyses of PM2.5-10 showed a positive correlation, increasing the risk of age-related cataracts. The study provides genetic evidence for the prevention and control of air pollution and highlights the importance of using multi-pollutant models to assess environmental health effects.
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.
目的:研究早产儿视网膜病变患儿经不同治疗措施后屈光状态的改变。方法:将72例(127眼)早产儿视网膜病变患儿按治疗方式分为3组:激光光凝组、注药(抗血管内皮生长因子药物)组和自然消退组。并于治疗前,治疗后1、4、7、12个月对其进行睫状肌麻痹检影验光,对比分析3组的球镜和等效球镜的差异。结果:在治疗后1、4、7及12个月,三组患儿的球镜度和等效球镜度的差异有统计学意义(P<0.05):注药组的球镜和等效球镜小于自然退化组及激光组(均P0.05)。治疗后12个月时激光光凝组、注药组和自然消退组近视发生率分别是2.4%、7.8%和2.0%,差异无统计学意义(P=0.356)。结论:经不同治疗措施的ROP患儿近视发生率无明显差异,但经玻璃体腔注射抗VEGF药物的ROP患儿正视化进程更快。
Objective: To observe the changes of refractive statues in infants with retinopathy of prematurity retinopathyof prematurity (ROP) after different treatments. Methods: According to different treatment methods, 72 cases(127 eyes) of infants with ROP were divided into 3 groups: laser photocoagulation group, intravitreal injectionof anti-vascular endothelial growth factor (VEGF) drugs group and natural regression group. Their sphere andspherical equivalent were measured by retinoscopy optometrist after the ciliary muscles paralyzed. The data beforetreatments and 1, 4, 7 and 12 months after treatments were recorded and analyzed. Results: The differences ofsphere and spherical equivalent among three groups were statistically significant: intravitreal injection of VEGFdrugs group was lower than natural regression group and the laser photocoagulation group, but there was no significant difference between natural regression group and laser photocoagulation group. Incidence of myopiaof laser photocoagulation, intravitreal injection of VEGF drugs, natural regression group were 2.4%, 7.8%, 2.0%,which was not statistically significant. Conclusion: There was no significant difference about the incidence rate ofmyopia among the three groups, but the emmetropization in infants with ROP after intravitreal injection of anti-VEGF drugs might be faster in the future.