Genome-wide gene-environment interaction study uncovers 162
vitamin D status variants using a precise ambient UVB measure
Shraim, R., Timofeeva, M., Wyse, C., van Geffen, J.,
van Weele, M., Romero-Ortuno, R. Lopez, L.M., Kleber, M.E.,
Pilz, S., März, W., Fletcher, B.S., Wilson, J.F.,
Theodoratou, E., Dunlop, M.G., McManus, R. and Zgaga, L.: 2025
Nature Communications 16, 10774, 12 pp.
doi: 10.1038/s41467-025-65820-x
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 (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.
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