Genetic correlation, causal relationship, and shared loci between vitamin D and COVID-19: A genome-wide cross-trait analysis

J Med Virol. 2023 May;95(5):e28780. doi: 10.1002/jmv.28780.


Observational studies have shown that vitamin D supplementation reduces the risk of COVID-19 infection, yet little is known about the shared genomic architectures between them. Leveraging large-scale genome-wide association study (GWAS) summary statistics, we investigated the genetic correlation and causal relationship between genetically determined vitamin D and COVID-19 using linkage disequilibrium score regression and Mendelian randomization (MR) analyses, and conducted a cross-trait GWAS meta-analysis to identify the overlapping susceptibility loci of them. We observed a significant genetic correlation between genetically predicted vitamin D and COVID-19 (rg = -0.143, p = 0.011), and the risk of COVID-19 infection would decrease by 6% for every 0.76 nmol L-1 increase of serum 25 hydroxyvitamin D (25OHD) concentrations in generalized MR (OR = 0.94, 95% CI: 0.89-0.99, p = 0.019). We identified rs4971066 (EFNA1) as a risk locus for the joint phenotype of vitamin D and COVID-19. In conclusion, genetically determined vitamin D is associated with COVID-19. Increased levels of serum 25OHD concentration may benefit the prevention and treatment of COVID-19.

Keywords: COVID-19; Mendelian randomization; genome-wide association study; molecular docking; vitamin D.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19* / epidemiology
  • Genome-Wide Association Study*
  • Humans
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Vitamin D
  • Vitamins


  • Vitamin D
  • Vitamins