| 摘要: |
| 目的 甲状腺功能与下丘脑-垂体-卵巢轴的分泌功能息息相关，目前甲状腺功能与卵巢储备功能之间的关系尚无定论，因此本研究采用孟德尔随机化方法探讨甲状腺功能障碍与卵巢功能不全或原发性卵巢功能衰竭（primary ovarian failure，POF）之间的因果关系。方法 从ThyroidOmics Consortium网站收集了促甲状腺激素（thyroid-stimulating hormone，TSH），总三碘甲状腺氨酸（total triiodothyronine，TT3），游离三碘甲状腺氨酸（free triiodothyronine，FT3），游离甲状腺素（free thyroxine，FT4），甲状腺过氧化物酶抗体（thyroid peroxidase antibody，TPOAb）等14项甲状腺相关激素的遗传关联数据，从FinnGen study收集卵巢功能不全（样本量为221279）和POF（样本量为219512）的遗传关联数据，以14个暴露相关的单核苷酸多态性作为工具变量，以卵巢功能不全和POF作为结局，以逆方差加权法（inverse-variance weighting, IVW）作为主要的因果推断方法，采用Cochran’s Q 检验异质性，MR-Egger回归检验水平多效性，孟德尔随机多态性残差和离群值检验(MR-PRESSO)和RadialMR检验离群值，采用MR-Egger、加权中位数法和加权模型分析结果的稳健性与可靠性。结果 IVW结果提示甲状腺功能亢进与卵巢功能不全之间存在潜在的正向因果关系（OR=1.10，95%CI：1.02-1.19，P=0.019），没有发现其他甲状腺相关激素水平与卵巢功能不全或POF之间存在因果关系的证据。结论 甲状腺功能亢进的遗传易感性可能与卵巢功能不全的发病风险有关，突出了青春期及育龄期女性筛查甲状腺功能的重要性。 |
| 关键词: 卵巢功能不全 原发性卵巢功能衰竭 甲状腺功能 甲亢 甲减 孟德尔随机化 |
| DOI： |
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| 基金项目:山东省中医药科技项目（M20241906） |
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| Causal Relationships Between Thyroid Dysfunction and Ovarian Dysfunction: A Two-Sample Mendelian Randomization Study |
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Xu Hui1,2,3,4,2,3,5, Jiang Quan6,7,5, Ma Wenlu8, Song Xu9, Xia Congmin6,7,5
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1.Guang&2.amp;3.#39;4.&5.an Men Hospital, China Academy of Chinese Medical Sciences, Beijing, China.;6.Guang'7.'8.The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine;9.Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine
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| Abstract: |
| Objective Thyroid function is closely related to the secretory function of the hypothalamic-pituitary-ovarian axis. However, the relationship between thyroid function and ovarian reverse function remains inconclusive. Therefore, this study employed Mendelian randomization (MR) to explore the causal relationship between thyroid dysfunction and ovarian dysfunction or primary ovarian failure (POF). Method Genetic association data for 14 thyroid-related hormones, including thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid peroxidase antibody (TPOAb), were collected from the ThyroidOmics Consortium. Genetic association data for ovarian dysfunction (sample size = 221,279) and POF (sample size = 219,512) were obtained from the FinnGen study. Fourteen exposure-related single nucleotide polymorphisms (SNPs) were used as instrumental variables, with ovarian dysfunction and POF as outcomes. The inverse-variance weighted (IVW) method was used as the primary causal inference approach. Heterogeneity was assessed using Cochran’s Q test, and horizontal pleiotropy was evaluated using MR-Egger regression. Outliers were identified using Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and RadialMR tests. Robustness and reliability of the results were verified using MR-Egger, weighted median, and weighted mode methods. Result The result of IVW showed potential positive causal relationship between hyperthyroidism and ovarian dysfunction (OR = 1.10, 95% CI: 1.02–1.19, P = 0.019). No evidence of a causal relationship was found between other thyroid-related hormone levels and ovarian dysfunction or POF. Conclusion Genetic susceptibility to hyperthyroidism may be associated with an increased risk of ovarian dysfunction, highlighting the importance of thyroid function screening in adolescent and reproductive-aged women. |
| Key words: Ovarian dysfunction Primary ovarian failure Thyroid function Hyperthyroidism Hypothyroidism Mendelian randomization |