基于孟德尔随机化研究血红蛋白浓度、甲状腺功能减退症、初产年龄与不良妊娠结局之间因果关系  

Study on causal relationship between hemoglobin concentration,hypothyroidism,age at first birth,and adverse pregnancy outcomes based on Mendelian randomization

作　　者：李倩 靳迎春 王海伟 Li Qian;Jin Yingchun;Wang Haiwei(Changzhi Maternal and Child Health Hospital Affiliated to Changzhi Medical College,Changzhi,Shanxi 046000,China;The Third Clinical School of Changzhi Medical College,Changzhi,Shanxi 046000,China)

机构地区：[1]长治医学院附属长治市妇幼保健院,山西长治046000 [2]长治医学院第三临床学院,山西长治046000

出　　处：《齐齐哈尔医学院学报》2024年第22期2118-2122,共5页Journal of Qiqihar Medical University

摘　　要：目的基于孟德尔随机化研究血红蛋白浓度、甲状腺功能减退症、初产年龄与不良妊娠结局之间因果关系。方法使用来自全基因组关联研究(Genome-wide association studies,GWAS)的大规模遗传汇总数据,包括血红蛋白浓度(Hemoglobin concentration,HB)、甲状腺功能减退症、初产年龄(Age at first birth,AFB)与不良妊娠结局,运用两样本孟德尔随机化法(Two-Sample Mendelian randomization,TSMR)和多变量孟德尔随机化(Multivariable Mendelian Randomization,MVMR)分析其因果关联。结果在TSMR分析中,AFB增加有助于降低不良妊娠结局的风险(OR=0.984,95%CI0.977~0.992,P=1.76×10^(-5))HB的遗传预测更高,甲状腺功能减退症可能增加其风险。HB、甲状腺功能减退症增加,不良妊娠结局也随之增加(OR=1.011,95%CI 1.002~1.021,P=0.019;OR=1.004,95%CI 1.000~1.009,P=0.038)。敏感性分析中,MVMR-Egger敏感性分析未发现水平多效性。与IVW-MVMR观察到的效果相似。MRPRESSO函数显示数据中未发现异常值,这意味着不存在可能影响异常校正MR分析结果的极端值。在中介MR分析中,AFB作为暴露因素,甲状腺功能减退症作为介质,不良妊娠结局作为结果。结论HB、甲状腺功能减退症和AFB与不良妊娠结局之间存在因果关系。甲状腺功能减退症可能是AFB造成不良妊娠结局发生的潜在介质。Objective To investigate the causal relationship between hemoglobin concentration,hypothyroidism,age at first birth,and adverse pregnancy outcomes using Mendelian randomization.Methods Large-scale genetic summary data from genome-wide association studies(GWAS)were utilized,encompassing hemoglobin concentration(HB),hypothyroidism,age at first birth(AFB),and adverse pregnancy outcomes.Causal associations were analyzed using Two-Sample Mendelian Randomization(TSMR)and Multivariable Mendelian Randomization(MVMR).Results In the TSMR analysis,an increase in AFB was associated with a reduced risk of adverse pregnancy outcomes(OR=0.984,95%CI 0.977~0.992,P=1.76×10^(-5)).A higher genetic prediction of HB and hypothyroidism was associated with an increased risk.As HB and hypothyroidism increased,so did the risk of adverse pregnancy outcomes(OR=1.011,95%CI 1.002~1.021,P=0.019;OR=1.004,95%CI 1.000~1.009,P=0.038).The MVMR-Egger sensitivity analysis did not detect horizontal pleiotropy.The findings were consistent with those observed in IVW-MVMR.The MRPRESSO function indicated no outliers in the data,suggesting that there were no extreme values that could potentially bias the adjusted MR analysis results.In the mediating MR analysis,AFB was considered the exposure factor,hypothyroidism the mediator,and adverse pregnancy outcomes the result.Conclusions There is a causal relationship between HB,hypothyroidism,and AFB with adverse pregnancy outcomes.Hypothyroidism may serve as a potential mediator for the adverse pregnancy outcomes associated with AFB.

关 键 词：血红蛋白浓度 甲状腺功能减退症 不良妊娠结局 初产年龄 

分 类 号：R714.21[医药卫生—妇产科学]