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

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.