The Impact of Vitamin D on Alzheimer's Disease: A Mendelian Randomization Study

Background Alzheimer's disease (AD) is a predominant neurodegenerative disorder affecting elderly people, but its pathogenesis has yet to be fully elucidated. An increasing body of evidence suggests a potential link between vitamin D deficiency and an elevated risk of AD. This study aimed to investigate the potential causal relationship between vitamin D levels and the risk of AD through Mendelian randomization analysis. Methods This study utilized two independent genome-wide association study (GWAS) datasets correlating vitamin D levels and AD. Single nucleotide polymorphisms (SNPs) significantly associated with vitamin D levels were selected as instrumental variables for the Mendelian randomization analysis. Multiple MR methods, including the inverse variance weighted (IVW) method, MR Egger, weighted median, simple mode, and weighted mode, were employed for the primary causal inference, complemented by heterogeneity tests and sensitivity analyses to assess the robustness of the results. Results IVW analysis indicated a significant inverse correlation between vitamin D levels and AD risk (β = -0.5725, 95% CI: -0.8349 to -0.3101, P = 0.0291), suggesting that an increase in vitamin D levels is associated with a reduction in AD risk. No significant heterogeneity was detected in the analysis. Conclusion This study provides preliminary evidence that vitamin D deficiency may contribute to an increased risk of AD. However, given the lack of consistent results from other MR methods, these findings should be interpreted with caution.