Abstract/Summary

Twin studies suggest a considerable genetic contribution to the variability in 25-hy-droxyvitamin D [25(OH)D] concentrations, reporting heritability estimates up to 80% in some stud-ies. While genome-wide association studies (GWAS) suggest notably lower rates (13-16%), they have identified many independent variants that associate with serum 25(OH)D concentrations. These discoveries have provided some novel insight into the metabolic pathway, and in this review we outline findings from GWAS studies to date with a particular focus on 35 variants which have provided replicating evidence for an association with 25(OH)D across independent large-scale anal-yses. Some of the 25(OH)D associating variants are linked directly to the vitamin D metabolic path-way, while others may reflect differences in storage capacity, lipid metabolism, and pathways re-flecting skin properties. By constructing a genetic score including these 25(OH)D associated variants we show that genetic differences in 25(OH)D concentrations persist across the seasons, and the odds of having low concentrations (<50 nmol/l) are about halved for individuals in the highest 20% of vitamin D genetic score compared to the lowest quintile, an impact which may have notable influ-ences on retaining adequate levels. We also discuss recent studies on personalized approaches to vitamin D supplementation and show how Mendelian randomization studies can help inform pub-lic health strategies to reduce adverse health impacts of vitamin D deficiency.