Abstract
Vitamin D and vitamin D receptor (
VDR)
have been postulated as environmental and genetic factors in neurodegeneration disorders including multiple sclerosis (MS), Alzheimer disease (AD), and recently Parkinson disease (PD). Given the sparse data on PD and
VDR
, we conducted a two-stage study to evaluate the genetic effects of
VDR
in PD. In the discovery stage, 30 tagSNPs in
VDR
were tested for association with PD risk as a discrete trait and age-at-onset of PD as a quantitative trait in 770 Caucasian PD families. In the validation stage, 18
VDR
SNPs were tested in an independent Caucasian cohort (267 cases and 267 controls) constructed from a genome-wide association study (GWAS). In the discovery dataset, SNPs in the 5′ end of
VDR
were associated with both risk and age-at-onset with more significant evidence of association with age-at-onset (nominal p=0.0008 for the most significant SNPs). These SNPs were also associated with AD in a recent GWAS. In the validation dataset, SNPs in the 3′ end of
VDR
were associated with age-at-onset (nominal p=0.003 for the most significant SNPs but not risk. The most significant 3′end SNP has been be associated with both MS and AD. Our findings suggest
VDR
as a potential susceptibility gene and support an essential role of vitamin D in PD.
