【摘要】 目的:利用双样本孟德尔随机化(MR)研究血浆蛋白与自然流产(SA)之间的因果关系。方法:使用来自冰岛人群的全基因组关联研究(GWAS)数据作为暴露因素，从芬兰基因研究项目(FinnGen)获得SA数据作为结局，使用MR研究分析血浆蛋白与SA发病风险之间的因果关系。以逆方差加权法(IVW)为主要研究方法，MR-Egger、加权中位数和加权模式对结果进行补充；并采用Cochrane′s Q检验、MR-Egger截距检验和留一法进行敏感性分析，验证数据的可靠性。结果:共有7种血浆蛋白可能与SA风险存在相关性，其中岩藻糖基转移酶10(FUT10)(OR 0.955,95%CI 0.915～0.996,P=0.034)、神经丛素B2(PLXNB2)(OR 0.947,95%CI 0.902～0.995,P=0.030)和白细胞介素-11Rα(IL-11 Rα)(OR 0.905,95%CI 0.848～0.966,P=0.003)水平升高与SA发病风险降低有关，而血浆蛋白可溶性L-选择素(SL-selectin)(OR 1.076,95%CI 1.021～1.134,P=0.006)、Cripto蛋白(OR 1.039,95%CI 1.008～1.071,P=0.012)、树突状细胞特异性细胞间黏附分子3抓取非整合素(DC-SIGN)(OR 1.051,95%CI 1.022～1.082,P=0.001)和蛋白Z依赖的蛋白酶抑制剂(ZPI)(OR 1.035,95%CI 1.001～1.071,P=0.045)水平升高与SA的发病风险升高有关。Cochrane′s Q检验P>0.05,MR-Egger截距检验P>0.05,留一法分析显示没有个别单核苷酸多态性对整个数据产生巨大的影响。结论:孟德尔随机化分析证实了多种血浆蛋白与SA之间存在因果关系，对研究血浆蛋白与SA之间的相关性具有潜在临床价值。更多还原

【Abstract】 Objective:To investigate the causal relationship between plasma proteins and spontaneous abortion using a two-sample Mendelian randomization method.Methods:Using genome-wide association study(GWAS) data from an Icelandic population as an exposure factor and spontaneous abortion data from the Finnish Genetic Research Project(FinnGen) as an outcome, the causal relationship between plasma proteins and the risk of developing spontaneous abortion was analyzed using a Mendelian randomization(MR) study.The inverse variance weighting(IVW) method was used as the primary study method, with MR-Egger, weighted median and weighted mode complementing the results; and sensitivity analyses were performed using Cochrane′s Q test, MR-Egger intercept testand leave-one-out method to validate the reliability of the data.Results:Seven plasma proteins were identified as potentially correlated with the risk of spontaneous abortion of which fucosyltransferase 10(FUT10)(OR 0.955,95%CI 0.915-0.996,P=0.034),plexin B2(PLXNB2)(OR 0.947,95%CI 0.902-0.995,P=0.030),and interleukin-11 receptor alpha(IL-11Rα)(OR 0.905,95%CI 0.848-0.966,P=0.003) were associated with a reduced risk of SA development, while plasma proteins soluble L-selectin(SL-selectin)(OR 1.076,95%CI 1.021-1.134,P=0.006),Cripto protein(OR 1.039,95%CI 1.008-1.071,P=0.012),dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin(DC-SIGN)(OR 1.051,95%CI 1.022-1.082,P=0.001),and protein Z-dependent protease inhibitor(ZPI)(OR 1.035,95%CI 1.001-1.071,P=0.045) levels were positively associated with the risk of developing SA.No heterogeneity or horizontal pleiotropy was detected(Cochrane’s Q test and MR-Egger intercept test, P>0.05),and leave-one-out analysis showed that there were no individual single-nucleotide polymorphisms that had a large impact on the overall data.Conclusions:This Mendelian randomization analyses confirmed the causal relationship between multiple plasma proteins and spontaneous abortion, which is potentially clinically valuable for studying the correlation between plasma proteins and spontaneous abortion.更多还原