Research paper
Genetically decreased vitamin D and risk of Alzheimer disease
Study answer
What this study found
A 1-SD decrease in genetically determined natural log-transformed 25OHD increased Alzheimer's disease odds by 25% (OR 1.25, 95% CI 1.03–1.51, p=0.021). Sensitivity analyses excluding potentially pleiotropic SNPs left results largely unchanged. Stratified analyses suggested stronger effects for metabolism-related SNPs (OR 1.46, 95% CI 1.03–2.07, p=0.032) than synthesis-related SNPs (OR 1.17, 95% CI 0.93–1.46, p=0.17). Conclusion: Vitamin D insufficiency likely causally increases AD risk; findings support investigating whether vitamin D supplementation could reduce AD risk in randomized…
- Study & population
- Two-sample Mendelian randomization using four SNPs for 25OHD from SUNLIGHT (N=33,996).
- Key limitation
- Potential residual pleiotropy and population stratification despite sensitivity analyses; IGAP’s case-control design; European ancestry limits generalizability; genetic instruments explain 2.44% of 25OHD variance; cannot define a precise protective 25OHD threshold; removal of GC or DHCR7 loci in sensitivity analyses…
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Open PDFOriginal abstract
Objective: To test whether genetically decreased vitamin D levels are associated with Alzheimer disease (AD) using mendelian randomization (MR), a method that minimizes bias due to confounding or reverse causation. Methods: We selected single nucleot…