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


Journal

The Journal of nutrition
ISSN: 1541-6100
Titre abrégé: J Nutr
Pays: United States
ID NLM: 0404243

Informations de publication

Date de publication:
01 02 2021
Historique:
received: 25 06 2020
revised: 26 08 2020
accepted: 13 11 2020
pubmed: 1 1 2021
medline: 11 5 2021
entrez: 31 12 2020
Statut: ppublish

Résumé

Genetic factors modify serum 25-hydroxyvitamin D [25(OH)D] concentration and can affect the optimal intake of vitamin D. We aimed to personalize vitamin D supplementation by applying knowledge of genetic factors affecting serum 25(OH)D concentration. 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. 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). 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.

Sections du résumé

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.

Identifiants

pubmed: 33382404
pii: S0022-3166(22)00056-6
doi: 10.1093/jn/nxaa391
doi:

Substances chimiques

Vitamin D 1406-16-2
25-hydroxyvitamin D A288AR3C9H

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

281-292

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.

Auteurs

Riitta J Sallinen (RJ)

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

Olga Dethlefsen (O)

National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Stockholm University, Stockholm, Sweden.

Sanni Ruotsalainen (S)

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.

Robert D Mills (RD)

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.

Timo A Miettinen (TA)

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.

Tuija E Jääskeläinen (TE)

Finnish Institute for Health and Welfare, Department of Public Health Solutions, Helsinki, Finland.

Annamari Lundqvist (A)

Finnish Institute for Health and Welfare, Department of Public Health Solutions, Helsinki, Finland.

Eero Kyllönen (E)

Physical and Rehabilitation Medicine Division, Oulu University Hospital, Oulu, Finland.

Heikki Kröger (H)

Department of Orthopaedics, Traumatology and Handsurgery, Kuopio University Hospital, Kuopio, Finland.
Kuopio Musculoskeletal Research Unit, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.

Jaro I Karppinen (JI)

Medical Research Center Oulu, University of Oulu and Oulu University Hospital, Oulu, Finland.
Finnish Institute of Occupational Health, Oulu, Finland.

Christel Lamberg-Allardt (C)

Department of Food and Nutrition, University of Helsinki, Helsinki, Finland.

Heli Viljakainen (H)

Department of Food and Nutrition, University of Helsinki, Helsinki, Finland.
Folkhälsan Research Center, Helsinki, Finland.

Mari A Kaunisto (MA)

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.

Olli Kallioniemi (O)

Institute for Molecular Medicine Finland (FIMM), HiLIFE, University of Helsinki, Helsinki, Finland.
Science for Life Laboratory, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.

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