Vitamin D levels vary seasonally with sunlight availability and with differences in diet. Seasonal variation of vitamin D levels is especially apparent at high latitudes where adequate sunlight may not be available, such as in Yup'ik Alaska Native communities living within the Arctic Circle (6633'N). Previous research has shown that a traditional diet high in marine-mammals and fish may contribute to the high levels of vitamin D in Yup'ik people, but recent trends show that the traditional diet intake is declining due to shifts to more Westernized foods, and this may result in vitamin D deficiency in Yup'ik young adults. Vitamin D deficiency is a widespread public health problem that is linked to increased risk for cancer, heart disease, and many other conditions. Despite evidence that variability in vitamin D (25(OH)D3) concentration is heritable, the current genetic literature only explains a small percentage of the heritability. This proposal seeks to identify and characterize genetic variation in vitamin D metabolism and regulatory genes and to look for associations with serum vitamin D (25(OH)D3) levels and traditional diet in a cross-section of Yup'ik Alaska Native volunteers. To this end, I propose to apply novel technologies to identify genomic sources of serum 25(OH)D3 variability and to explore Yup'ik people's perceptions, understandings, and expectations for research involving genomic medicine. These findings will advance our understanding of vitamin D insufficiency; identify the facilitators and barriers to genomic research involving Yup'ik people; and position academic research collaborators to address current and future health priorities and concerns with precision medicine technologies in Alaska Native people.

Public Health Relevance

Vitamin D deficiency is a widespread public health problem that is linked to increased risk for cancer, heart disease, infections, rickets, and osteoporosis. The global aim of my research is to elucidate the role of variation in diet and genes involved in vitamin D homeostasis and their relationship to serum vitamin D levels. This work will provide insight into the mechanisms of vitamin D homeostasis, to better understand how individuals within populations are affected by changing diet, lifestyles and genetic predisposition.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM119237-02
Application #
9307553
Study Section
Special Emphasis Panel (ZRG1-F06-S (20)L)
Program Officer
Barski, Oleg
Project Start
2016-06-01
Project End
2019-05-31
Budget Start
2017-06-01
Budget End
2018-05-31
Support Year
2
Fiscal Year
2017
Total Cost
$57,066
Indirect Cost
Name
University of Washington
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Henderson, Lindsay M; Claw, Katrina G; Woodahl, Erica L et al. (2018) P450 Pharmacogenetics in Indigenous North American Populations. J Pers Med 8:
Claw, Katrina G; Anderson, Matthew Z; Begay, Rene L et al. (2018) A framework for enhancing ethical genomic research with Indigenous communities. Nat Commun 9:2957
Tanner, Julie-Anne; Zhu, Andy Z; Claw, Katrina G et al. (2018) Novel CYP2A6 diplotypes identified through next-generation sequencing are associated with in-vitro and in-vivo nicotine metabolism. Pharmacogenet Genomics 28:7-16
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Tanner, Julie-Anne; Prasad, Bhagwat; Claw, Katrina G et al. (2017) Predictors of Variation in CYP2A6 mRNA, Protein, and Enzyme Activity in a Human Liver Bank: Influence of Genetic and Nongenetic Factors. J Pharmacol Exp Ther 360:129-139
Xu, Meijuan; Bhatt, Deepak Kumar; Yeung, Catherine K et al. (2017) Genetic and Nongenetic Factors Associated with Protein Abundance of Flavin-Containing Monooxygenase 3 in Human Liver. J Pharmacol Exp Ther 363:265-274
Chen, Ling-Ling; Claw, Katrina G; Ramachandran, Sohini (2016) A two-fold challenge: the experience of women of color in genomics. Genome Biol 17:210