Common genetic determinants of vitamin D deficiency

19 July 2010

Vitamin D deficiency affects more than a billion people worldwide, and causes rickets, accelerated age-related bone loss, and may also contribute to numerous common diseases including diabetes, cancer and cardiovascular disease. Although social, cultural and environmental factors are known affect vitamin D status – most notably, exposure to sunlight and dietary supplementation – twin studies suggest that genetic factors are also important, with heritability estimates of around 50%.

An international, multicentre consortium has now published the findings of a large genome-wide association study (GWAS) involving nearly 34,000 individuals from 15 cohorts of European descent, which aimed to find common genetic variants affecting vitamin D concentration and risk of insufficiency [Wang TJ et al. Lancet (2010 376: 180-7]. In addition to genotyping genome-wide common variants and a small selection of candidate genes, the concentration of circulating 25-hydroxyvitamin D and vitamin D binding protein were measured and analysed along with age, sex, season and body-mass index. Common variants (SNPs) at three genetic loci reached the genome-wide significance threshold, all located near genes involved in vitamin D transport and metabolism. After correcting for other factors, these variants were also found to increase the risk of vitamin D insufficiency.

Comment: As an accompanying news article highlights, the study is published against a backdrop of continuing international debate over public health policy regarding exposure to sunlight, in order to balance risk of skin cancer against that of vitamin D deficiency [Lancet (2010) 376:142]. This study is unlikely to have an impact on that debate; while the GWAS is notable for its large study size and attention to technical detail, the usefulness of the findings are currently unclear. Further work is needed to understand whether this genetic predisposition modifies the response to sun exposure or dietary intake of vitamin D, and how it affects response to treatment. Nonetheless, these findings will improve our biological understanding of how the body processes vitamin D - for example, as the accompanying Editorial points out, it is somewhat surprising that none of the genes identified are linked with skin pigmentation, which is known to be a major factor in vitamin D status [Bouillon R, Lancet (2010) 376:148-9]. Ultimately, this new molecular level of biological understanding could lead to improved treatments. 

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