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

Abstract 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 ( r g = −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.