血浆血管内皮生长因子家族蛋白与前置胎盘的因果关联:孟德尔随机化研究

Casual association between plasma vascular endothelial growth factor family proteins and placenta praevia:a Mendelian randomization study

目的:利用两样本孟德尔随机化(MR)方法探究血浆血管内皮生长因子(VEGF)家族蛋白与前置胎盘之间的因果关联。方法:在UK Biobank和IEU数据库中选择血浆VEGF家族蛋白的全基因组关联研究(GWAS)数据,在芬兰基因组数据库FinnGen中选择前置胎盘的GWAS数据,根据设定的阈值筛选工具变量,采用逆方差加权法(IVW)、MR-Egger、加权中位数法和加权模型进行两样本MR分析,其中IVW作为主要分析方法。进行Cochran's Q检验验证MR结果的异质性,MR-Egger回归和MR-PRESSO法评估结果的水平多效性,留一法验证结果的敏感性。结果:血浆VEGFA与前置胎盘的高风险具有因果关联(P<0.05,OR>1),血浆VEGFB、VEGFC、VEGFD和胎盘生长因子(PLGF)均与前置胎盘的风险无因果关联。Cochran's Q检验显示MR分析结果无异质性。MR-Egger回归和MR-PRESSO法显示不存在水平多效性。留一法结果显示没有任何单一的工具变量会对MR分析结果产生强烈影响。结论:血浆VEGFA与前置胎盘之间存在因果关联,检测血浆VEGFA对于预测前置胎盘可能具有临床意义。

Objective:To explore the causal association between plasma vascular endothelial growth factor(VEGF)family proteins and placenta praevia using a two-sample Mendelian randomization(MR)analysis.Methods:Genome-wide association study(GWAS)data of plasma VEGF family proteins were obtained from the UK Biobank and IEU database,and the GWAS data of placenta praevia were obtained from the FinnGen database.The instrument variables were screened out according to the set threshold.Two-sample MR analysis was performed using inverse-variance weighted(IVW),MR-Egger,weighted median,and weighted mode method,with IVW as the primary analysis method.Cochran's Q test was employed for testing heterogeneity of the results.MR-Egger regression and MR-PRESSO method were conducted to assess horizontal pleiotropy of the results.The leave-one-out method was employed to verify the sensitivity of the results.Results:Plasma VEGFA was causally associated with an increased risk of placenta praevia(P<0.05,OR>1),while plasma VEGFB,VEGFC,VEGFD and placental growth factor(PLGF)were not causally associated with the risk of placenta praevia.Cochran's Q test showed that there was no heterogeneity in the results of the MR analysis.MR-Egger regression and MR-PRESSO method showed that there was no horizontal pleiotropy in the results of the MR analysis.Leave-one-out method demonstrated that no single instrumental variable strongly influenced the MR results.Conclusion:The present study indicates a causal association between plasma VEGFA and placenta praevia,suggesting that detecting plasma VEGFA may have clinical significance for predicting placenta praevia.