Common Genetic Determinants of Vitamin D Insufficiency: A Genome-Wide Association Study
Abstract
Environmental disorders associated with vitamin D deficiency include musculoskeletal disorders (childhood rickets, osteomalacia, and fractures), and may include extraskeletal disorders (diabetes, cardiovascular disease, risk of falls, and cancer). There is high interindividual variability in the occurrence of both musculoskeletal and extraskeletal disorders. Previous twin and family studies suggested that genetic factors play a significant role in this variability. Little data exist on the possible effects of common genetic variation on vitamin D status; the available studies have been small and only small numbers of variants were examined. The SUNLIGHT consortium (study of underlying genetic determinants of vitamin D and highly related traits) was a multicenter genome-wide association study designed to identify common genetic variants that affect vitamin D concentrations and increase the risk of vitamin D insufficiency. Concentrations of vitamin D were determined in 33,996 individuals of European descent from 15 epidemiologic cohorts. Of these cohorts, 5 were designated as discovery cohorts (n = 16,125), 5 as in-silico replication cohorts (n = 9367), and 5 as de novo replication cohorts (n = 8504). Genome-wide analyses were conducted in all cohorts. Methods used to measure 25-hydroxyvitamin D concentrations varied between cohorts and included radioimmunoassay, chemiluminescent assay, enzyme-linked immunosorbent assay, or mass spectrometry. Concentrations lower than 75…
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