Vitamin D levels and risk of type 1 diabetes: A Mendelian randomization study

source extracted confidence: high 2026-04-09
#diabetes-mellitus-type-1 #diabetes-mellitus-type-2 #genome-wide-association-study #humans #mendelian-randomization-analysis

Vitamin D levels and risk of type 1 diabetes: A Mendelian randomization study

Manousaki et al., 2021 | PLoS Med | Rct

Citation

Manousaki Despoina, Harroud Adil, ... Richards J Brent. Vitamin D levels and risk of type 1 diabetes: A Mendelian randomization study. PLoS Med. 2021-Feb;18(2):e1003536. doi:10.1371/journal.pmed.1003536

Abstract

BACKGROUND: Vitamin D deficiency has been associated with type 1 diabetes in observational studies, but evidence from randomized controlled trials (RCTs) is lacking. The aim of this study was to test whether genetically decreased vitamin D levels are causally associated with type 1 diabetes using Mendelian randomization (MR). METHODS AND FINDINGS: For our two-sample MR study, we selected as instruments single nucleotide polymorphisms (SNPs) that are strongly associated with 25-hydroxyvitamin D (25OHD) levels in a large vitamin D genome-wide association study (GWAS) on 443,734 Europeans and obtained their corresponding effect estimates on type 1 diabetes risk from a large meta-analysis of 12 type 1 diabetes GWAS studies (Ntot = 24,063, 9,358 cases, and 15,705 controls). In addition to the main analysis using inverse variance weighted MR, we applied 3 additional methods to control for pleiotropy (MR-Egger, weighted median, and mode-based estimate) and compared the respective MR estimates. We also undertook sensitivity analyses excluding SNPs with potential pleiotropic effects. We identified 69 lead independent common SNPs to be genome-wide significant for 25OHD, explaining 3.1% of the variance in 25OHD levels. MR analyses suggested that a 1 standard deviation (SD) decrease in standardized natural log-transformed 25OHD (corresponding to a 29-nmol/l change in 25OHD levels in vitamin D-insufficient individuals) was not associated with an increase in type 1 diabetes risk (inverse-variance weighted (IVW) MR odds ratio (OR) = 1.09, 95% CI: 0.86 to 1.40, p = 0.48). We obtained similar results using the 3 pleiotropy robust MR methods and in sensitivity analyses excluding SNPs associated with serum lipid levels, body composition, blood traits, and type 2 diabetes. Our findings indicate that decreased vitamin D levels did not have a substantial impact on risk of type 1 diabetes in the populations studied. Study limitations include an inability to exclude the existence of smaller associations and a lack of evidence from non-European populations. CONCLUSIONS: Our findings suggest that 25OHD levels are unlikely to have a large effect on risk of type 1 diabetes, but larger MR studies or RCTs are needed to investigate small effects.

Key Findings

For our two-sample MR study, we selected as instruments single nucleotide polymorphisms (SNPs) that are strongly associated with 25-hydroxyvitamin D (25OHD) levels in a large vitamin D genome-wide association study (GWAS) on 443,734 Europeans and obtained their corresponding effect estimates on type 1 diabetes risk from a large meta-analysis of 12 type 1 diabetes GWAS studies (Ntot = 24,063, 9,358 cases, and 15,705 controls). In addition to the main analysis using inverse variance weighted MR, w

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition diabetes

MeSH Terms

  • Diabetes Mellitus, Type 1
  • Diabetes Mellitus, Type 2
  • Genome-Wide Association Study
  • Humans
  • Mendelian Randomization Analysis
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • Vitamin D
  • Vitamin D Deficiency

Evidence Classification

  • Level: Rct
  • Publication Types: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
  • Vertical: vitamin-d-autoimmune

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09