女性生殖行为与类风湿性关节炎的因果关系:一项孟德尔随机化研究  

Causal relationship between female reproductive behavior and rheumatoid arthritis:a Mendelian randomization study

作　　者：刘晨茜 汪娅蓓 汪悦[2] LIU Chenxi;WANG Yabei;WANG Yue(The First Clinical School of Nanjing University of Chinese Medicine,Nanjing 210023,P.R.China;Jiangsu Provincial Hospital of Traditional Chinese Medicine,Nanjing 210029,P.R.China)

机构地区：[1]南京中医药大学第一临床医学院,南京210023 [2]江苏省中医院,南京210029

出　　处：《中国循证医学杂志》2024年第10期1149-1155,共7页Chinese Journal of Evidence-based Medicine

摘　　要：目的采用两样本孟德尔随机化方法探讨女性生殖行为与类风湿性关节炎(rheumatoid arthritis,RA)的因果关系,以期为临床防治提供理论依据。方法在大型公开可检索的数据库中获取全基因关联分析汇总数据,选取4个与生殖行为相关的特征(初潮、绝经、首次妊娠年龄和末次妊娠年龄)作为暴露因素,RA作为结局因素,筛选出与暴露因素表型强相关的单核苷酸多态性作为工具变量,进行两样本孟德尔随机化分析,以评估暴露与疾病之间的潜在因果关系。结果(1)两样本孟德尔随机化的逆方差加权法结果显示,首次妊娠年龄和末次妊娠年龄都与RA发病风险呈负向因果关系[OR=0.91,95%CI(0.85,0.98),P=0.011;OR=0.54,95%CI(0.31,0.93),P=0.026],初潮和绝经与RA无因果关系。敏感性分析结果表明以上因果关系稳健,MR-Egger intercept分析未检测到潜在的水平多效性(P首次妊娠年龄-RA=0.169,P末次妊娠年龄-RA=0.283)。(2)反向孟德尔随机化分析显示,RA与首次妊娠年龄存在正向因果关联,与末次妊娠年龄不存在因果关系[OR=1.07,95%CI(1.02,1.11),P=0.001]。(3)多变量孟德尔随机化结果显示,女性首次妊娠年龄与RA风险呈负向因果关系[OR=0.88,95%CI(0.80,0.97),P=0.010],女性末次妊娠年龄也与RA风险呈负向因果关系[OR=0.68,95%CI(0.48,0.97),P=0.033]。(4)女性怀孕年龄与患RA的风险之间存在负相关关系,提示其具有潜在的保护作用。结论妊娠年龄可能与RA发病风险呈负相关的因果关系,初潮和绝经与RA无因果关系。Objective To investigate the potential causal relationship between four types of reproductive behaviors and rheumatoid arthritis(RA),with the goal of establishing a theoretical foundation for clinical prevention and treatment strategies.Methods Pooled gene-wide association study(GWAS)data were obtained from large publicly searchable databases.Four characteristics like menarche,menopause,the age of first pregnancy and the age of last pregnancy,which related to reproductive behavior were selected as the exposure factors and RA as the outcome factors.Single nucleotide polymorphisms(SNPs),which were strongly correlated with the phenotype of the exposure factors,were screened as the instrumental variables,and two-sample Mendelian randomization analyses were used to assess the potential causal relationship between the exposure and the disease.Results(1)The Mendelian randomization analysis utilizing the inverse variance weighted method on two distinct samples revealed a significant negative correlation between the age of first pregnancy and last pregnancy with the risk of RA(OR=0.91,95%CI 0.85 to 0.98,P=0.011;OR=0.54,95%CI0.31 to 0.93,P=0.026).Conversely,no causal relationship was observed between menarche and menopause with RA.Sensitivity analysis confirmed the robustness of the causal relationship,while MR Egger intercept analysis did not identify any potential horizontal pleiotropy(P_(age of first gestation-RA)=0.169,P_(age of last gestation-RA)=0.283).(2)Reverse Mendelian randomization analysis revealed a significant positive causal association between RA and the age of first pregnancy,while no causal relationship was observed with the age of last pregnancy(OR=1.07,95%CI 1.02 to 1.11,P=0.001).(3)Multivariate Mendelian randomization analysis demonstrated that both the age of first pregnancy and last pregnancy in women were inversely associated with the risk of RA(OR=0.88,95%CI 0.80 to 0.97,P=0.010;OR=0.68,95%CI 0.48 to 0.97,P=0.033).(4)There existed a negative correlation between the age of pregnancy in women and the

关 键 词：孟德尔随机化 生殖行为 类风湿性关节炎 因果推断 

分 类 号：R593.22[医药卫生—内科学]