孟德尔随机化研究甲状腺功能与抗苗勒管激素水平的关系。
Mendelian randomization study of thyroid function and anti-Müllerian hormone levels.
机构信息
Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
出版信息
Front Endocrinol (Lausanne). 2023 Jul 20;14:1188284. doi: 10.3389/fendo.2023.1188284. eCollection 2023.
OBJECTIVE
Although previous studies have reported an association between thyroid function and anti-Müllerian hormone (AMH) levels, which is considered a reliable marker of ovarian reserve, the causal relationship between them remains uncertain. This study aims to investigate whether thyrotropin (TSH), free thyroxine (fT4), hypo- and hyperthyroidism are causally linked to AMH levels.
METHODS
We obtained summary statistics from three sources: the ThyroidOmics Consortium (N = 54,288), HUNT + MGI + ThyroidOmics meta-analysis (N = 119,715), and the most recent AMH genome-wide association meta-analysis (N = 7,049). Two-sample MR analyses were conducted using instrumental variables representing TSH and fT4 levels within the normal range. Additionally, we conducted secondary analyses to explore the effects of hypo- and hyperthyroidism. Subgroup analyses for TSH were also performed.
RESULTS
MR analyses did not show any causality relationship between thyroid function and AMH levels, using normal range TSH, normal range fT4, subclinical hypothyroidism, subclinical hyperthyroidism and overt hypothyroidism as exposure, respectively. In addition, neither full range TSH nor TSH with individuals <50 years old was causally associated with AMH levels. MR sensitivity analyses guaranteed the robustness of all MR results, except for the association between fT4 and AMH in the no-+ group.
CONCLUSION
Our findings suggest that there was no causal association between genetically predicted thyroid function and AMH levels in the European population.
目的
尽管先前的研究报告了甲状腺功能与抗苗勒管激素（AMH）水平之间的关联，而 AMH 被认为是卵巢储备的可靠标志物，但它们之间的因果关系仍不确定。本研究旨在调查促甲状腺激素（TSH）、游离甲状腺素（fT4）、甲状腺功能减退症和甲状腺功能亢进症是否与 AMH 水平存在因果关系。
方法
我们从三个来源获得了汇总统计数据：甲状腺 Omics 联盟（N=54288）、HUNT+MGI+甲状腺 Omics 荟萃分析（N=119715）和最近的 AMH 全基因组关联荟萃分析（N=7049）。使用代表正常范围内 TSH 和 fT4 水平的工具变量进行两样本 MR 分析。此外，我们还进行了二次分析来探索甲状腺功能减退症和甲状腺功能亢进症的影响。还进行了 TSH 的亚组分析。
结果
MR 分析表明，使用正常范围内的 TSH、正常范围内的 fT4、亚临床甲状腺功能减退症、亚临床甲状腺功能亢进症和显性甲状腺功能减退症作为暴露因素，甲状腺功能与 AMH 水平之间没有因果关系。此外，全范围 TSH 或年龄<50 岁的 TSH 与 AMH 水平均无因果关系。MR 敏感性分析保证了除 fT4 与 no-+组中的 AMH 之间的关联外，所有 MR 结果的稳健性。
结论
我们的研究结果表明，在欧洲人群中，遗传预测的甲状腺功能与 AMH 水平之间没有因果关系。
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