Genetic Mediators of Celiac Disease and Premature Ovarian Failure: Hypothyroidism and Systemic Lupus Erythematosus

IF 2.5 3区医学 Q3 IMMUNOLOGY

American Journal of Reproductive Immunology Pub Date : 2025-01-28 DOI:10.1111/aji.70038

Yuxi Hou, Weihong Song, Guoguo Wei, Yuanhang Mo, Manna Zhang, Xiaohu Chen, Chunge Cao, Chaoyan Yue, Xiaowen Shao

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Abstract

Background

Observational studies suggested celiac disease (CD) possibly be a risk factor for premature ovarian failure (POF). However, causality remains unclear. And hypothyroidism and systemic lupus erythematosus may be the mediating factors.

Methods

We performed 2-sample Mendelian randomization (2SMR) to infer a causal relationship between CD and POF using genome-wide association study summary data obtained from IEU OpenGWAS database and FinnGen R12 database. Inverse-variance weighted method was used as the main analysis of MR. Heterogeneity was measured based on Cochran's Q value. We used the Two-Step MR to analyze whether hypothyroidism and SLE are mediators of the causal relationship between CD and POF. Summary level data of the hypothyroidism and SLE were obtained from IEU OpenGWAS.

Results

Genetically predicted CD may increase the risk of POF by 16% (odds ratio [OR]: 1.16, 95% CI: 1.06–1.26, p = 0.001). Hypothyroidism and SLE could mediate 13.46% and 26.36% of the association between CD and POF, respectively (p = 0.038, p = 0.025).

Conclusions

Our study revealed that CD has a positive contribution effect on POF. CD can elevate the risk of POF by 16%. Besides, hypothyroidism and SLE played a partial mediating role in the causal relationship between the two.

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乳糜泻和卵巢早衰的遗传介质：甲状腺功能减退和系统性红斑狼疮。

背景：观察性研究提示乳糜泻（CD）可能是卵巢早衰（POF）的危险因素。然而，因果关系尚不清楚。甲状腺功能减退和系统性红斑狼疮可能是其中介因素。方法：我们使用来自IEU OpenGWAS数据库和FinnGen R12数据库的全基因组关联研究汇总数据，进行2样本孟德尔随机化（2SMR）来推断CD和POF之间的因果关系。采用反方差加权法对mr进行主要分析，以Cochran’s Q值衡量异质性。我们使用两步磁共振分析甲状腺功能减退和SLE是否是CD和POF之间因果关系的中介。甲状腺功能减退和SLE的汇总水平数据来自IEU OpenGWAS。结果：基因预测的CD可能使POF的风险增加16%（优势比[OR]: 1.16, 95% CI: 1.06-1.26, p = 0.001）。甲状腺功能减退和SLE分别介导CD和POF相关性的13.46%和26.36% （p = 0.038, p = 0.025）。结论：本研究显示CD对POF有积极的贡献作用。乳糜泻可使POF的风险增加16%。此外，甲状腺功能减退和SLE在两者的因果关系中起部分中介作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American Journal of Reproductive Immunology 医学-免疫学

CiteScore

6.20

自引率

5.60%

发文量

314

审稿时长

2 months

期刊介绍： The American Journal of Reproductive Immunology is an international journal devoted to the presentation of current information in all areas relating to Reproductive Immunology. The journal is directed toward both the basic scientist and the clinician, covering the whole process of reproduction as affected by immunological processes. The journal covers a variety of subspecialty topics, including fertility immunology, pregnancy immunology, immunogenetics, mucosal immunology, immunocontraception, endometriosis, abortion, tumor immunology of the reproductive tract, autoantibodies, infectious disease of the reproductive tract, and technical news.