焦虑、抑郁、神经质与复发性流产的因果关系:一项孟德尔随机化研究  

Causal relationships of anxiety,depression and neuroticism with recurrent spontaneous abortion:a Mendelian randomization analysis

作　　者：袁昊 李霄[1,2] 孙志玉 卫爱武 YUAN Hao;LI Xiao;SUN Zhiyu;WEI Aiwu(Departmental of Reproductive Medicine,First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou,Henan;the First Clinical Medical School of Henan University of Chinese Medicine,Zhengzhou,Henan,China)

机构地区：[1]河南中医药大学第一附属医院生殖医学科,郑州 [2]河南中医药大学第一临床医学院,郑州

出　　处：《陆军军医大学学报》2025年第4期378-384,F0003,共8页Journal of Army Medical University

基　　金：河南省自然科学基金(232300420058,222300420226)。

摘　　要：目的分别探究焦虑、抑郁、神经质等3种负面情绪与复发性流产之间的因果关系。方法利用全基因组关联研究数据提取与焦虑、抑郁、神经质密切相关的遗传位点作为工具变量,分别利用逆方差加权法、加权中位数法、加权众数法及MR-Egger回归法进行孟德尔随机化分析,评价焦虑、抑郁、神经质与复发性流产之间的因果效应,并进行异质性、基因多效性与敏感性分析。结果从全基因组关联研究(genome-wide association study,GWAS)数据中提取共46个SNPs作为工具变量(焦虑数据5个,抑郁数据9个,神经质数据32个),经逆方差加权法、加权中位数法、加权众数法及MR-Egger回归法计算OR值与95%CI,焦虑数据结果分别为1.07(0.86~1.32)、1.10(0.85~1.43)、1.14(0.81~1.59)、1.18(0.53~2.61),抑郁数据结果分别为1.11(0.93~1.32)、1.05(0.83~1.32)、0.96(0.67~1.38)、0.57(0.25~1.31),神经质数据结果分别为1.01(0.75~1.36)、1.07(0.73~1.56)、1.02(0.49~2.12)、2.40(0.46~12.44),上述因果分析均无统计学意义(P均>0.05);经可靠性分析,异质性评价Cochran’sQ检验差异不具有显著性(P均>0.05),基因多效性评价MR-Egger回归截距均接近于0(P均>0.05),敏感性评价留一法检验后合并因果效应值相近。结论焦虑、抑郁、神经质与复发性流产之间不存在因果关联,可靠性检验提示结果相对稳健。Objective To explore the causal relationships of anxiety,depression and neuroticism with recurrent spontaneous abortion(RSA).Methods Genome-wide association study(GWAS)data were used to extract single nucleotide polymorphisms(SNPs)closely related to anxiety,depression and neuroticism as instrumental variables(IVs).Inverse variance weighting(IVW),weighted median estimator(WME),weighted mode(WM)and Mendelian randomization(MR)-Egger regression were employed for MR analysis to evaluate the causal effects of anxiety,depression and neuroticism with RSA,and to analyze heterogeneity,gene pleiotropy and sensitivity.Results A total of 46 SNPs were extracted from GWAS data as IVs(5 anxiety SNPs,9 depression SNPs,and 32 neuroticism SNPs).IVW,WME,WM and MR-Egger regression analysis revealed that the odds ratio(OR)and 95%confidence interval(CI)of anxiety data were 1.07(0.86-1.32),1.10(0.85-1.43),1.14(0.81-1.59)and 1.18(0.53-2.61);those of depression data were 1.11(0.93-1.32),1.05(0.83-1.32),0.96(0.67-1.38)and 0.57(0.25-1.31);those of neuroticism data were 1.01(0.75-1.36),1.07(0.73-1.56),1.02(0.49-2.12)and 2.40(0.46-12.44),but none of the above causal analyses were statistically significant(all P>0.05).After reliability analysis,the Cochran's Q test for heterogeneity evaluation was not significant(P>0.05),the MR-Egger regression intercepts for gene pleiotropy evaluation were all close to 0(P>0.05),and the sensitivity evaluation"Leave-one-out"test also shows that the combined causal effect values are similar.Conclusion There dose not exist causal relationships of anxiety,depression and neuroticism with RSA.The reliability test shows that the results are relatively robust.

关 键 词：负面情绪 复发性流产 孟德尔随机化 

分 类 号：R395.1[哲学宗教—心理学] R714.4[医药卫生—医学心理学]