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


    Shraim, Rasha, Timofeeva, Maria, Wyse, Cathy, van Geffen, Jos, van Weele, Michiel, Romero-Ortuno, Roman, Lopez, Lorna M., Kleber, Marcus E., Pilz, Stefan, März, Winfried, Fletcher, Benjamin S., Wilson, James F., Theodoratou, Evropi, Dunlop, Malcolm G., McManus, Ross and Zgaga, Lina (2025) Genome-wide gene-environment interaction study uncovers 162 vitamin D status variants using a precise ambient UVB measure. Nature Communications, 16 (1). ISSN 2041-1723

    Abstract

    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 (h 2 Q1 = 8.48% vs . h 2 Q5 = 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 Type: Article
    Keywords: Genome-wide gene-environment interaction; 162 vitamin D status variants; ambient UVB measure;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 21245
    Identification Number: 10.1038/s41467-025-65820-x
    Depositing User: Lorna Lopez
    Date Deposited: 26 Feb 2026 14:35
    Journal or Publication Title: Nature Communications
    Publisher: Nature Publshing Group
    Refereed: Yes
    Related URLs:
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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