• The Journal of nutrition · Feb 2021

    Genetic Risk Score for Serum 25-Hydroxyvitamin D Concentration Helps to Guide Personalized Vitamin D Supplementation in Healthy Finnish Adults.

    • Riitta J Sallinen, Olga Dethlefsen, Sanni Ruotsalainen, Robert D Mills, Timo A Miettinen, Tuija E Jääskeläinen, Annamari Lundqvist, Eero Kyllönen, Heikki Kröger, Jaro I Karppinen, Christel Lamberg-Allardt, Heli Viljakainen, Mari A Kaunisto, and Olli Kallioniemi.
    • Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
    • J. Nutr. 2021 Feb 1; 151 (2): 281-292.

    BackgroundGenetic factors modify serum 25-hydroxyvitamin D [25(OH)D] concentration and can affect the optimal intake of vitamin D.ObjectivesWe aimed to personalize vitamin D supplementation by applying knowledge of genetic factors affecting serum 25(OH)D concentration.MethodsWe performed a genome-wide association study of serum 25(OH)D concentration in the Finnish Health 2011 cohort (n = 3339) using linear regression and applied the results to develop a population-matched genetic risk score (GRS) for serum 25(OH)D. This GRS was used to tailor vitamin D supplementation for 96 participants of a longitudinal Digital Health Revolution (DHR) Study. The GRS, serum 25(OH)D concentrations, and personalized supplementation and dietary advice were electronically returned to participants. Serum 25(OH)D concentrations were assessed using immunoassays and vitamin D intake using FFQs. In data analyses, cross-sectional and repeated-measures statistical tests and models were applied as described in detail elsewhere.ResultsGC vitamin D-binding protein and cytochrome P450 family 2 subfamily R polypeptide 1 genes showed genome-wide significant associations with serum 25(OH)D concentration. One single nucleotide polymorphism from each locus (rs4588 and rs10741657) was used to develop the GRS. After returning data to the DHR Study participants, daily vitamin D supplement users increased from 32.6% to 60.2% (P = 6.5 × 10-6) and serum 25(OH)D concentration from 64.4 ± 20.9 nmol/L to 68.5 ± 19.2 nmol/L (P = 0.006) between August and November. Notably, the difference in serum 25(OH)D concentrations between participants with no risk alleles and those with 3 or 4 risk alleles decreased from 20.7 nmol/L to 8.0 nmol/L (P = 0.0063).ConclusionsWe developed and applied a population-matched GRS to identify individuals genetically predisposed to low serum 25(OH)D concentration. We show how the electronic return of individual genetic risk, serum 25(OH)D concentrations, and factors affecting vitamin D status can be used to tailor vitamin D supplementation. This model could be applied to other populations and countries.© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.

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