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.

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“…We used inverse variance weighted (IVW) as a primary approach, namely combining the Wald ratio estimates of each SNP instrument, and supplemented IVW method with IVW radial. 11,12 We further performed MR-Egger and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) analyses to remove the influence of pleiotropy. 11,13 MR-Egger allows all SNP instruments to have pleiotropic effects, but the pleiotropy effects should be independent of the SNP-exposure association.…”