Abstract
BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder, primarily characterized by motor impairments. Vitamin D has several regulatory functions in nerve cell survival and gene expression via its receptors. Although research has shown that vitamin D deficiency is prevalent among PD patients, the causal link to PD risk remains unclear. This study aims to investigate the causal relationship between vitamin D and PD using a bidirectional two-sample Mendelian randomization (MR) analysis method. METHODS: This study applied a bidirectional two-sample MR analysis to explore the causal link between vitamin D and PD. We selected statistically significant single nucleotide polymorphisms (SNPs) related to 25-hydroxyvitamin D (25(OH)D) as instrumental variables (IVs), ensuring no association with known confounders. The analysis used GWAS data from over 1.2 million Europeans across four major published datasets, elucidating the genetic correlation between vitamin D levels and PD. RESULTS: We identified 148 instrumental SNPs associated with 25(OH)D. After adjustment for confounding-related SNPs, 131 SNPs remained in the analysis. Data from three PD cohorts revealed no significant correlation between 25(OH)D levels and PD risk using the IVW method (Pcohort1 = 0.365, Pcohort2 = 0.525, Pcohort3 = 0.117). The reverse MR analysis indicated insufficient evidence of PD causing decreased vitamin D levels (P = 0.776). CONCLUSION: This is the first study to use bidirectional MR across three PD cohorts to investigate the causal relationship between vitamin D and PD. The results indicate that vitamin D levels are not significantly causally related to PD risk at the genetic level. Therefore, future studies should exercise caution when investigating the relationship between vitamin D levels and PD risk. While no direct causal link exists between vitamin D levels and PD, this does not preclude the potential of vitamin D levels as a biomarker for PD diagnosis. Furthermore, larger-scale longitudinal studies are necessary to evaluate the diagnostic and predictive value of vitamin D levels in PD.