Potential Causal Association Between Follicle-Stimulating Hormone and Alzheimer's Disease: Genetic Loci Study and Mendelian Randomization Study.

IF 1.2 4区生物学 Q4 GENETICS & HEREDITY

Annals of Human Genetics Pub Date : 2025-07-17 DOI:10.1111/ahg.70004

Chenchen Ding, Xiaohong Xu, Bangliang Xu, Jiali Wu

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引用次数: 0

Abstract

Background: Alzheimer's disease (AD) predominantly affects older women, with research suggesting elevated follicle-stimulating hormone (FSH) levels in postmenopausal women correlate with AD risk and cognitive decline. Understanding the causal relationship between FSH and AD is essential.

Materials and methods: We selected single-nucleotide polymorphisms (SNPs) linked to FSH as instrumental variables (IVs) for Mendelian randomization (MR). Statistical methods, including inverse variance weighted (IVW), MR Egger, Weighted Median, Weighted Mode, and Simple Mode, were employed to assess causality and potential pleiotropy. Shared genetic loci between FSH and AD were explored.

Results: We carefully identified and utilized a total of 20 valid SNPs as IVs to assess the potential causal relationship between FSH and AD. Our analysis revealed a significant causal association between genetically determined FSH levels and AD [beta = -0.004; OR = 0.996, 95% confident interval (CI): 0.994-0.999; p = 0.002]. We successfully identified 20 SNPs that correspond to 8 differentially expressed genes (DEGs) between AD and non-demented (ND). These genes have not been previously reported to be linked to either FSH or AD. We conducted an in-depth analysis to explore the potential roles of these genes in the context of FSH and AD.

Conclusion: Our MR study revealed that FSH potentially has a causal association with AD. Additionally, FSH might possess distinctive biological mechanisms that influence the development of AD.

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促卵泡激素与阿尔茨海默病之间的潜在因果关系：基因位点研究和孟德尔随机化研究。

背景：阿尔茨海默病（AD）主要影响老年妇女，研究表明绝经后妇女卵泡刺激素（FSH）水平升高与AD风险和认知能力下降有关。了解促卵泡刺激素和AD之间的因果关系至关重要。材料和方法：我们选择与FSH相关的单核苷酸多态性（snp）作为孟德尔随机化（MR）的工具变量（IVs）。采用反方差加权（IVW）、MR Egger、加权中位数、加权模式和简单模式等统计方法来评估因果关系和潜在的多效性。探讨了FSH和AD之间共享的遗传位点。结果：我们仔细识别并利用了总共20个有效的snp作为IVs来评估FSH和AD之间的潜在因果关系。我们的分析显示，基因决定的FSH水平与AD之间存在显著的因果关系[β = -0.004；OR = 0.996, 95%可信区间（CI）： 0.994-0.999；p = 0.002]。我们成功地鉴定了20个snp，对应于AD和非痴呆（ND）之间的8个差异表达基因（DEGs）。这些基因之前没有报道与卵泡刺激素或AD相关。我们进行了深入的分析，以探索这些基因在FSH和AD背景下的潜在作用。结论：我们的MR研究显示FSH可能与AD有因果关系。此外，FSH可能具有影响AD发展的独特生物学机制。

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

Annals of Human Genetics 生物-遗传学

CiteScore

4.20

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Annals of Human Genetics publishes material directly concerned with human genetics or the application of scientific principles and techniques to any aspect of human inheritance. Papers that describe work on other species that may be relevant to human genetics will also be considered. Mathematical models should include examples of application to data where possible. Authors are welcome to submit Supporting Information, such as data sets or additional figures or tables, that will not be published in the print edition of the journal, but which will be viewable via the online edition and stored on the website.