子痫前期与甲状腺功能减退的双向因果关系:来自孟德尔随机化的遗传证据  

Bidirectional Causality Between Preeclampsia and Hypothyroidism:Genetic Evidence from Mendelian Randomization

作　　者：张烨潇 王一枭 吴丹[1] 周秀丽 乌兰 ZHANG Yexiao;WANG Yixiao;WU Dan;ZHOU Xiuli;WU Lan(Department of Obstetrics,Women's Hospital of Nanjing Medical University(Nanjing Women and Children's Healthcare Hospital),Nanjing 210000,China)

机构地区：[1]南京医科大学附属妇产医院(南京市妇幼保健院)产科,南京210000

出　　处：《西南医科大学学报》2024年第3期206-209,共4页Journal of Southwest Medical University

基　　金：国家自然科学基金(82101781)。

摘　　要：目的通过孟德尔随机化(mendelian randomization,MR)方法分析子痫前期(pre-eclampsia,PE)与甲状腺功能减退之间是否存在因果关系。方法从Finngen数据库获取PE和甲状腺功能减退数据集,提取工具变量(instrumental variable,IV),应用逆方差加权法等5种MR方法探究PE与甲状腺功能减退之间的因果关系。运用Cochran's Q、MR-Egger回归、MR-PRESSO、留一法等敏感性分析方法评价研究结果的稳定性和可靠性。结果逆方差加权法结果表明,PE与甲状腺功能减退之间没有因果关系(OR=1.024,95%CI:0.965~1.087,P=0.435),而甲状腺功能减退和PE风险之间存在潜在的正向因果关系(OR=1.097,95%CI:1.006~1.196,P=0.036)。其余四种MR分析方法表明甲状腺功能减退和PE风险之间的因果关系稳定。Cochrane's Q统计结果表明纳入的各IV之间不存在显著异质性,MR-Egger截距法和MRPRESSO法均未发现纳入的IV存在显著的水平多效性。但是,留一法结果表明多个IV在甲状腺功能减退和PE风险之间的因果关系中发挥决定性作用。结论本研究从遗传学角度切入,应用MR方法揭示了甲状腺功能减退和PE之间的因果关系,为子痫前期高风险人群的个性化管理和精准医疗提供了理论依据。Objective To analyze whether there is a causal association between pre-eclampsia and hypothyroidism by Mendelian randomization methods.Methods The pre-eclampsia and hypothyroidism data sets were obtained from the Finngen database,instru⁃mental variables were extracted,and five Mendelian randomization methods including the inverse variance weighting method were ap⁃plied to explore the causal association between pre-eclampsia and hypothyroidism.Sensitivity analyses such as Cochran's Q,MREgger regression,MR-PRESSO,and leave-one-out method were applied to evaluate the stability and reliability of the study results.Re⁃sults The results of the inverse variance weighting method showed that there was no causal association between pre-eclampsia and hypo⁃thyroidism(OR=1.024,95%CI:0.965-1.087,P=0.435),whereas there was a potentially positive causal association between hypothy⁃roidism and pre-eclampsia risk(OR=1.097,95%CI:1.006-1.196,P=0.036).The remaining four Mendelian randomization analyses showed a stable causal relationship between hypothyroidism and risk of preeclampsia.Cochrane's Q statistical results showed that there was no significant heterogeneity among the included instrumental variables.Neither the MR-Egger intercept method nor the MRPRESSO method found significant horizontal pleiotropy among the included instrumental variables.However,leave-one-out results sug⁃gested that multiple instrumental variables played a decisive role in the causal association between hypothyroidism and risk of preeclampsia.Conclusions This study revealed the causal association between hypothyroidism and pre-eclampsia by applying the Mende⁃lian randomization method from the perspective of genetics,which provided a theoretical basis for the personalized management and treatment of people at high risk of pre-eclampsia.

关 键 词：甲状腺功能减退 子痫前期 双向孟德尔随机化 因果关系 

分 类 号：R54[医药卫生—心血管疾病]