Relationships between 25-Hydroxyvitamin D and Alpha-synucleinopathies: A Mendelian Randomization Study

  1. Fu-Jia Li
  2. Ru-Lin Geng
  3. Cheng Wen
  4. Kai-Xun Huang
  5. Dan-Yu Lin
  6. Zhong-Gui Li
  7. Jie-Li Zhang
  8. Chuan-Ying Xu
  9. Wei Zhang
  10. Jie Zu
  11. Li-Guo Dong
  12. Wen-Xin Wang
  13. Zhi-Jia Ruan
  14. Pei-Xiao Yin
  15. Chen-Yang Guan
  16. Gui-Yun Cui
  17. En-Xiang Tao
0 evaluations Published on
Read the full article Related papers
This article on Sciety

Abstract

Background

Alpha-synucleinopathies, including Parkinson’s disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), are neurodegenerative diseases characterized by abnormal aggregation of alpha-synuclein. Isolated REM sleep behavior disorder (iRBD) is a prodromal stage of these disorders. While 25-hydroxyvitamin D (25[OH]D) has been linked to PD in previous studies, its causal role remains unclear, and its relationship with iRBD, MSA, and DLB is rarely explored.

Objectives

This study used Mendelian randomization (MR) to investigate the causal relationship between 25(OH)D and iRBD, PD, MSA, and DLB.

Methods

GWAS data for 25(OH)D were sourced from the UK Biobank, and outcome data for PD were obtained from the latest FinnGen R12 database. Data for iRBD, PD onset age, PD clinical progression, MSA, and DLB were derived from a broader European population. The study had two steps: univariable MR (UVMR) using genome-wide IV selection as the primary analysis, with replication analyses using biological function-based IV selection and sunlight exposure and vitamin D supplementation-related factors as exposures. Multivariable MR (MVMR) was then conducted to adjust for 13 covariates, testing the robustness of findings.

Results

25(OH)D showed a significant protective effect on MSA across all UVMR (both primary and replication) and MVMR analyses. It also exhibited a nominal protective effect on PD in the Finnish population in primary UVMR analysis, but this was not replicated. No associations were found between 25(OH)D and iRBD, PD onset age, PD clinical progression, or DLB. Power analyses indicated insufficient sensitivity to detect weak effects of 25(OH)D on iRBD and DLB.

Conclusions

MR analysis supports a protective role of 25(OH)D against MSA. While nominally protective for PD in the Finnish population, the effect was not robust. Weak effects on iRBD and DLB cannot be excluded.

Related articles

Related articles are currently not available for this article.