No association between genetically predicted vitamin D levels and Parkinson's disease

PLoS One. 2024 Nov 15;19(11):e0313631. doi: 10.1371/journal.pone.0313631. eCollection 2024.

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.

MeSH terms

  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Mendelian Randomization Analysis*
  • Parkinson Disease* / blood
  • Parkinson Disease* / genetics
  • Polymorphism, Single Nucleotide*
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / genetics
  • Vitamin D* / analogs & derivatives
  • Vitamin D* / blood

Substances

  • Vitamin D
  • 25-hydroxyvitamin D

Grants and funding

This research was supported by the Autonomous Region Key Research and Development Project (Grant No. 2023B03003), the Tian-Shan Talent Program (Grant No. 2022TSYCLJ0066), the National Natural Science Foundation of China (Grant No. 82371258), and the Central Guiding Local Science and Technology Development Special Fund Project (Grant No. ZYYD2022C17). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.