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Genes Nutr. 2016 Aug 2;11:23. doi: 10.1186/s12263-016-0538-y. eCollection 2016.

Linkage and association analysis of circulating vitamin D and parathyroid hormone identifies novel loci in Alaska Native Yup'ik people.

Author information

1
Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL USA.
2
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL USA ; Department of Biology, King University, Bristol, TN USA.
3
Department of Health Outcomes and Policy, College of Medicine, University of Florida, Gainesville, FL USA.
4
Center for Alaska Native Health Research, Institute of Arctic Biology, University of Alaska Fairbanks, Fairbanks, AK USA.
5
Departments of Molecular Biosciences and Nutrition, University of California at Davis, Davis, CA USA.
6
Department of Pharmaceutics, University of Washington, Seattle, WA USA.
7
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL USA.

Abstract

BACKGROUND:

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, 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.

METHODS:

We 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.

RESULTS:

We 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.

CONCLUSION:

We 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.

KEYWORDS:

Alaska Native; Linkage; Parathyroid hormone; Vitamin D; n-3 fatty acids

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