严重急性呼吸综合征冠状病毒2型感染与视网膜血管阻塞之间不存在因果关系:来自两样本孟德尔随机化证据

No causal relationship between SARS-CoV-2 infection and retinal vascular occlusion:evidence from two-sample mendelian randomization studies

目的孟德尔随机化(MR)分析严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)感染与视网膜血管阻塞的因果关系。方法采用欧洲人群全基因组关联研究(GWAS)的汇总统计数据,进行双样本MR分析。SARS-CoV-2感染的GWAS数据包含SARS-CoV-2普通感染、感染住院、重症感染者,分别为2597856、2095324、1086211例。视网膜血管阻塞数据来自FinnGen数据库,其中视网膜动脉阻塞、视网膜静脉阻塞(RVO)分别为203269、182945例。采用逆方差加权(IVW)、随机效应模型、加权中位数(WM)、MR-Egger、简单模式、加权模式分析SARS-CoV-2不同感染表型与视网膜血管阻塞之间的双向因果关系。采用Q统计量的P值判断分析各单核苷酸多态性(SNP)之间是否存在异质性;采用MR多态性残差和离群值(MR-Presso)法检测SNP异常值;采用MR-Egger截距测试检验SNP的水平多效性。结果MR分析IVW、随机效应模型、MR-Egger、WM、加权模式结果显示,SARS-CoV-2普通感染、感染住院、重症感染与视网膜血管阻塞无显著关联(P>0.05);视网膜血管阻塞与SARS-CoV-2不同感染表型无显著关联(P>0.05)。简单模式下,SARS-CoV-2重症感染与RVO存在关联(P<0.05);RVO与SARS-CoV-2普通感染存在关联(P<0.05)。IVW、MR-Egger未观察到不同暴露与结局存在异质性(P>0.05)。MR-Egger无水平多效性证据(P>0.05);MR-Presso未发现离群的SNP。结论本研究结果不支持SARS-CoV-2感染与视网膜血管阻塞发生存在因果关系。

Objective To analyze the causal relationship between SARS-CoV-2 infection and retinal vascular obstruction by mendelian randomization(MR).Methods A two-sample MR analysis utilizing summary statistics from genome-wide association studies(GWAS)in European populations was conducted.The GWAS data for SARS-CoV-2 infection comprised cases of common infection(2597856),hospitalized infection(2095324),and severe infection(1086211).Data on retinal vascular obstruction were obtained from the FinnGen database,which included 203269 cases of retinal artery obstruction and 182945 cases of retinal vein obstruction(RVO).Inverse variance weighting(IVW),random effects models,weighted median(WM),MREgger regression,simple models,and weighted models were used to analyze the bidirectional causal relationship between different SARS-CoV-2 infection phenotypes and retinal obstruction.The Q statistic was used to assess heterogeneity among single nucleotide polymorphisms(SNP),while MR-Presso was utilized to detect SNP outliers,and MR-Egger intercept tests were performed to evaluate horizontal pleiotropy.Results The MR analysis,using IVW,random effects models,MR-Egger,WM,and weighted models,indicated no significant association between common SARS-CoV-2 infection, hospitalized infection, severe infection, and retinalvascular obstruction (P>0.05). Additionally, retinal vascular obstruction did not show a significant associationwith the various SARS-CoV-2 infection phenotypes (P>0.05). In the simple model, a significant associationwas found between severe SARS-CoV-2 infection and RVO (P<0.05), as well as between RVO and commonSARS-CoV-2 infection (P<0.05). No heterogeneity was observed in the IVW and MR-Egger analyses(P>0.05). The MR-Egger test provided no evidence of horizontal pleiotropy (P>0.05), and MR-Presso detectedno outlier SNP. Conclusion The findings of this study do not support a causal relationship between SARSCoV-2 infection and the occurrence of retinal vascular obstruction.