University of Oulu

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, Olli Kallioniemi, on behalf of the Digital Health Revolution Project, Genetic Risk Score for Serum 25-Hydroxyvitamin D Concentration Helps to Guide Personalized Vitamin D Supplementation in Healthy Finnish Adults, The Journal of Nutrition, Volume 151, Issue 2, February 2021, Pages 281–292,

Genetic risk score for serum 25-hydroxyvitamin D concentration helps to guide personalized vitamin D supplementation in healthy Finnish adults

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Author: Sallinen, Riitta J.1,2; Dethlefsen, Olga3; Ruotsalainen, Sanni1;
Organizations: 1Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland
2Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
3National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Stockholm University, Stockholm, Sweden
4Finnish Institute for Health and Welfare, Department of Public Health Solutions, Helsinki, Finland
5Physical and Rehabilitation Medicine Division, Oulu University Hospital, Oulu, Finland
6Department of Orthopaedics, Traumatology and Handsurgery, Kuopio University Hospital, Kuopio, Finland
7Kuopio Musculoskeletal Research Unit, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland
8Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland
9Finnish Institute of Occupational Health, Oulu, Finland
10Department of Food and Nutrition, University of Helsinki, Helsinki, Finland
11Folkhälsan Research Center, Helsinki, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 0.3 MB)
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Language: English
Published: Oxford University Press, 2021
Publish Date: 2022-02-23


Background: Genetic factors modify serum 25-hydroxyvitamin D [25(OH)D] concentration and can affect the optimal intake of vitamin D.

Objectives: We aimed to personalize vitamin D supplementation by applying knowledge of genetic factors affecting serum 25(OH)D concentration.

Methods: We 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.

Results: GC 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).

Conclusions: We 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.

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Series: Journal of nutrition
ISSN: 0022-3166
ISSN-E: 1541-6100
ISSN-L: 0022-3166
Volume: 151
Issue: 2
Pages: 281 - 292
DOI: 10.1093/jn/nxaa391
Type of Publication: A1 Journal article – refereed
Field of Science: 1184 Genetics, developmental biology, physiology
3142 Public health care science, environmental and occupational health
Funding: This research was supported by a grant from Tekes (Business Finland)—the Finnish Funding Agency for Innovation—as part of the Digital Health Revolution (DHR) program. The research group led by OK was also supported by the Sigrid Jusélius Foundation, Academy of Finland, and Knut and Alice Wallenberg Foundation.
Copyright information: © The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition. This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (