Serum Parathyroid Hormone, 25-Hydroxyvitamin D, and Risk of Alzheimer's Disease: A Mendelian Randomization Study

Abstract

We conducted Mendelian randomization analyses to investigate the associations of serum parathyroid hormone (S-PTH) and serum 25-hydroxyvitamin D (S-25OHD) concentrations with Alzheimer's disease (AD). Five and seven single nucleotide polymorphisms associated with S-PTH and S-25OHD concentrations, respectively, were used as instrumental variables. Data for AD were acquired from the International Genomics of Alzheimer's Project (17,008 AD cases and 37,154 controls). Genetically higher S-PTH concentrations were not associated with AD (odds ratio per standard deviation increase in S-PTH = 1.11; 95% CI 0.97⁻1.26; p = 0.12). In contrast, all seven 25OHD-increasing alleles were inversely associated with AD and two of the associations were statistically significant (p < 0.05). The odds ratio of AD per genetically-predicted one standard deviation increase in S-25OHD was 0.86 (95% CI 0.78⁻0.94; p = 0.002). This study provides evidence that vitamin D may play a role in AD but found no significant association between S-PTH and AD.

Keywords: Alzheimer’s disease; Mendelian randomization; parathyroid hormone; vitamin D.

Figure 1

Association between a genetically-predicted one standard deviation increase of S-PTH concentration and AD.

Figure 2

Association between a genetically predicted one standard deviation increase of S-25OHD concentration and Alzheimer’s disease. rs1968487 was used as proxy SNP for rs10745742 (r² between these two SNPs = 1.0).