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Genome-wide gene-environment interaction study uncovers 162 vitamin D status variants using a precise ambient UVB measure

Vitamin D status is influenced by genetic and environmental factors—primarily sun exposure. Using satellite weather data, we estimated an ambient UVB dose for each participant based on residential address and date of sampling. We conducted genome-wide tests in 338,977 UK Biobank White British partic...

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Main Authors: Shraim, Rasha (Author) , Timofeeva, Maria (Author) , Wyse, Cathy (Author) , van Geffen, Jos (Author) , van Weele, Michiel (Author) , Romero-Ortuno, Roman (Author) , Lopez, Lorna M. (Author) , Kleber, Marcus E. (Author) , Pilz, Stefan (Author) , März, Winfried (Author) , Fletcher, Benjamin S. (Author) , Wilson, James F. (Author) , Theodoratou, Evropi (Author) , Dunlop, Malcolm G. (Author) , McManus, Ross (Author) , Zgaga, Lina (Author)
Format: Article (Journal)
Language:English
Published: 28 November 2025
In: Nature Communications
Year: 2025, Volume: 16, Pages: 1-12
ISSN:2041-1723
DOI:10.1038/s41467-025-65820-x
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-025-65820-x
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-025-65820-x
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Author Notes:Rasha Shraim, Maria Timofeeva, Cathy Wyse, Jos van Geffen, Michiel van Weele, Roman Romero-Ortuno, Lorna M. Lopez, Marcus E. Kleber, Stefan Pilz, Winfried März, Benjamin S. Fletcher, James F. Wilson, Evropi Theodoratou, Malcolm G. Dunlop, Ross McManus & Lina Zgaga
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Summary:Vitamin D status is influenced by genetic and environmental factors—primarily sun exposure. Using satellite weather data, we estimated an ambient UVB dose for each participant based on residential address and date of sampling. We conducted genome-wide tests in 338,977 UK Biobank White British participants, adjusted for age, sex, supplements, UVB dose, and 10 principal components to account for population structure. We applied three models to test for genetic effects: marginal only, main and interaction, and joint effects. We identified 307 variants associated with standardised log-transformed 25-hydroxyvitamin D (25OHD) concentration, 162 of which were not previously identified in GWAS. We identify an increase in SNP-heritability by increasing ambient UVB exposure quintiles (h2Q1 = 8.48% vs. h2Q5 = 15.56%). Downstream annotation implicated genes in the 25OHD pathway, including the circadian regulator, BMAL1. This and further findings suggest that vitamin D status and circadian rhythm may be entangled and that vitamin D metabolites may have a role as mediators of seasonal physiological fluctuations, including metabolism, and in turn explain the established associations with lipid metabolism pathways.
Item Description:Gesehen am 13.01.2026
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-025-65820-x

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