Genetic determinants of 25-hydroxyvitamin D concentrations

Heritability estimates from twin studies suggest a considerable genetic contribution to the variability in 25(OH)D concentrations, with estimates as high as 86% reported by some studies. Genome-wide association studies have identified a large number of independent variants associated with 25(OH)D concentrations, providing novel insight into the determinants and metabolic pathway contributing to 25(OH)D concentrations in the circulation. In this chapter, we review and describe the key genetic variants associated with 25(OH)D, focusing on genes for which the evidence has been replicated in independent studies, for many of which we have evidence for a role in the canonical vitamin D pathway. We discuss the uses of this information, including the prospects related to personalized approaches to vitamin D supplementation.