Genetic determinants of 25-hydroxyvitamin D concentrations and their relevance to public health

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 (