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Title: Multi-ethnic analysis shows genetic risk and environmental predictors interact to influence 25(OH)D concentration and optimal vitamin D intake

Author
item HATCHELL, KATHRYN - University Of Wisconsin
item LU, QIONGSHI - University Of Wisconsin
item MARES, JULIE - University Of Wisconsin
item MICHOS, ERIN - Johns Hopkins University School Of Medicine
item WOOD, ALEXIS - Children'S Nutrition Research Center (CNRC)
item ENGELMANN, CORINNE - University Of Wisconsin

Submitted to: Genetic Epidemiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/27/2019
Publication Date: 12/12/2019
Citation: Hatchell, K.E., Lu, Q., Mares, J.A., Michos, E.D., Wood, A.C., Engelmann, C.D. 2019. Multi-ethnic analysis shows genetic risk and environmental predictors interact to influence 25(OH)D concentration and optimal vitamin D intake. Genetic Epidemiology. https://doi.org/10.1002/gepi.22272.
DOI: https://doi.org/10.1002/gepi.22272

Interpretive Summary: Low levels of Vitamin D predict poor health outcomes such as obesity, type 2 diabetes and cardiovascular disease (CVD). Although vitamin D levels are influenced by environmental factors such as exposure to sunlight and dietary vitamin D, we know people respond to these factors differently. Some people can absorb vitamin D from their diet well, while other have more difficulty. To better understand why some children are at risk of low vitamin D levels, we gave individuals a single score reflecting the sum of their genotypes across all genes currently known to influence vitamin D levels. In data from three very large, well characterized studies, we found that that there was a significant interaction between this score and dietary vitamin D intake on vitamin D levels in the blood in Caucasians, but not in African-Americans; i.e. we identified the first genetic score which can predict how well an individual absorbs vitamin D from their diet for those with Caucasian ancestry. As genotyping becomes less expensive and more well known, it is used more and more in clinical settings. These results may therefore help us predict who is at risk of Vitamin D insufficiency and allow us to effectively target supplementation and prevent the adverse health outcomes associated with low vitamin D levels.

Technical Abstract: 25-Hydroxyvitamin D (25(OH)D) concentration is a complex trait with genetic and environmental predictors that may determine how much vitamin D exposure is required to reach optimal concentration. Interactions between continuous measures of a polygenic score (PGS) and vitamin D intake (PGS*intake) or available ultraviolet (UV) radiation (PGS*UV) were evaluated in individuals of African (n=1,099) or European (n=8,569) ancestries. Interaction terms and joint effects (main and interaction terms) were tested using one-degree of freedom (1-DF) and 2-DF models, respectively. Models controlled for age, sex, body mass index, cohort, and dietary intake/available UV. In addition, in participants achieving Institute of Medicine (IOM) vitamin D intake recommendations, 25(OH)D was evaluated by level PGS. The 2-DF PGS*intake, 1-DF PGS*UV, and 2-DF PGS*UV results were statistically significant in participants of European ancestry (p=3.3x10**-18, p=2.1x10**-2, and p=2.4x10**-19, respectively), but not in those of African ancestry. In European-ancestry participants reaching IOM vitamin D intake guidelines, the percent of participants achieving adequate 25(OH)D (>=20 ng/ml) increased as genetic risk decreased (72% vs. 89% in highest vs. lowest risk; p=.018). Available UV radiation and vitamin D intake interact with genetics to influence 25(OH)D. Individuals with higher genetic risk may require more vitamin D exposure to maintain optimal 25(OH)D concentrations.