Abstract
BackgroundVitamin D deficiency is a well-documented public health issue with both genetic and environmental determinants. Populations living at far northern latitudes are vulnerable to vitamin D deficiency and its health sequelae, although consumption of traditional native dietary pattern rich in fish and marine mammals may buffer the effects of reduced sunlight exposure. To date, few studies have investigated the genetics of vitamin D metabolism in circumpolar populations or considered genediet interactions with fish and n-3 fatty acid intake.MethodsWe searched for genomic regions exhibiting linkage and association with circulating levels of vitamin D and parathyroid hormone (PTH) in 982 Yup’ik individuals from the Center for Alaska Native Health Research Study. We also investigated potential interactions between genetic variants and a biomarker of traditional dietary intake, the δ15N value.ResultsWe identified several novel regions linked with circulating vitamin D and PTH as well as replicated a previous linkage finding on 2p16.2 for vitamin D. Bioinformatic analysis revealed multiple candidate genes for both PTH and vitamin D, including CUBN, MGAT3, and NFKBIA. Targeted association analysis identified NEBL as a candidate gene for vitamin D and FNDC3B for PTH. We observed significant associations between a variant in MXD1 and vitamin D only when an interaction with the δ15N value was included. Finally, we integrated pathway level information to illustrate the biological validity of the proposed candidate genes.ConclusionWe provide evidence of linkage between several biologically plausible genomic regions and vitamin D metabolism in a circumpolar population. Additionally, these findings suggest that a traditional dietary pattern may modulate genetic effects on circulating vitamin D.Electronic supplementary materialThe online version of this article (doi:10.1186/s12263-016-0538-y) contains supplementary material, which is available to authorized users.
Highlights
Vitamin D deficiency is a well-documented public health issue with both genetic and environmental determinants
red blood cell (RBC) δ15N values and circulating parathyroid hormone (PTH) were both significantly higher among women, while 25(OH)D levels did not vary by gender
This study presents novel evidence of linkage between several biologically plausible genomic regions and 25(OH)D/PTH in a study population of Yup’ik people with seasonally low exposure to sunlight and high intake of vitamin D-rich foods
Summary
Vitamin D deficiency is a well-documented public health issue with both genetic and environmental determinants. Populations living at far northern latitudes are vulnerable to vitamin D deficiency and its health sequelae, consumption of traditional native dietary pattern rich in fish and marine mammals may buffer the effects of reduced sunlight exposure. Few studies have investigated the genetics of vitamin D metabolism in circumpolar populations or considered genediet interactions with fish and n-3 fatty acid intake. Vitamin D, a steroid hormone synthesized in the skin or acquired through diet, and parathyroid hormone (PTH), secreted by parathyroid glands, work synergistically to promote absorption of dietary calcium and phosphates (reviewed by [31]). In addition to the environmental inputs of sunlight and diet, high inter-individual variation in circulating 25(OH)D as well as family studies suggest a role for genetic determinants [1, 14]. Despite the documented importance of ancestry to vitamin D status [42, 46], genetic risk factors for other populations are less established
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