Common Genetic Determinants of Vitamin D Insufficiency: A Genome-Wide Association Study

Abstract

Background-Vitamin D is crucial for maintaining musculoskeletal health. Recently, vitamin D insufficiency has been linked to a number of extraskeletal disorders, including diabetes, cancer, and cardiovascular disease. Determinants of circulating 25-hydroxyvitamin D (25-OH D) include sun exposure and dietary intake, but its high heritability suggests that genetic determinants may also play a role.Methods-We performed a genome-wide association study of 25-OH D among ∼30,000 individuals of European descent from 15 cohorts. Five cohorts were designated as discovery cohorts (n=16,125), five as in silico replication cohorts (n=9,366), and five as de novo replication * rs2282679 in Framingham, rs4588 in 1958 Birth Cohort (r 2 between SNPs >0.99).

Insufficient autumn vitamin D intake and low vitamin D status in 7-year-old Icelandic children

“…Studies have shown the correlation between consumption of vitamin D and vitamin D status to be about r 5 0?20-0?54 for children over 12 years of age, which suggests that the variability in vitamin D status in the blood is only partly explained by vitamin D consumption (19) . Furthermore, only about a quarter of the inter-individual variability in serum vitamin D concentration is considered to be attributable to season, latitude or reported vitamin D intake (26) . Data from the Northern Ireland Young Hearts 2000 study found that the strongest predictors of vitamin D inadequacy during winter for children aged 12-15 years were low vitamin D intake and gender (7) , which is not in line with our results as vitamin D status did not differ between genders in present study during the autumn season, despite different intake levels.…”

Optimal vitamin D levels in Crohn's disease: a review

“…Moreover, genetic variants in vitamin D hydroxylation and transport may also contribute substantially to both the development of vitamin D insufficiency and poor response to supplementation (47) .…”

Is vitamin D in rheumatoid arthritis a magic bullet or a mirage? The need to improve the evidence base prior to calls for supplementation

“…However, given the above-described limitations in epidemiologic studies of vitamin D, RCTs are needed to enable investigators to prove or disprove the notion of a causal role of vitamin D in RA (or other chronic diseases). Mendelian randomization studies may also offer insights into causal pathways, and appropriate genetic determinants of vitamin D deficiency to facilitate such studies have recently been identified (55). In an era of evidence-based medicine, proof of causality is vital before widespread public health programs of supplementation are implemented.…”