️ Episode 243: Genome-wide UVB GxE study finds 162 vitamin D variants
In this episode of PaperCast Base by Base, we explore A GWIS of 338,977 UK Biobank White British participants using a cumulative weighted ambient UVB measure identified 307 independent loci for 25-hydroxyvitamin D, including 162 novel variants
Study Highlights:The study linked a cumulative and weighted ambient UVB (CW-D-UVB) dose from TEMIS to each participant’s residence and blood draw date to model gene-environment interaction on standardized log-transformed 25OHD in 338,977 White British UK Biobank participants. Genome-wide marginal, interaction, and joint tests identified 307 independent variants associated with 25OHD, 162 of which were novel to prior GWAS. SNP-heritability increased across CW-D-UVB quintiles from 8.48% in the lowest to 15.56% in the highest and was higher in participants reporting ≥3 hours outdoors. Functional annotation implicated known vitamin D genes, glucuronidation and lipid metabolism pathways, and circadian clock genes including BMAL1 and NPAS2, with replication showing concordant effect directions in European, LURIC, and ORCADES cohorts
Conclusion:Incorporating a precise ambient UVB exposure measure increased power to detect genetic effects on vitamin D status and revealed GxE interactions linking vitamin D biology with lipid metabolism and circadian regulation
Music:Enjoy the music based on this article at the end of the episode.
Reference:Shraim R, Timofeeva M, Wyse C, van Geffen J, van Weele M, Romero-Ortuno R, Lopez LM, Pilz S, März W, Fletcher BS, Kleber ME, Wilson JF, Theodoratou E, Dunlop MG, McManus R, Zgaga L. Genome-wide gene-environment interaction study uncovers 162 vitamin D status variants using a precise ambient UVB measure. Nat Commun. 2025;16:10774. https://doi.org/10.1038/s41467-025-65820-x
License:This episode is based on an open-access article published under the Creative Commons Attribution 4.0 International License (CC BY 4.0) – https://creativecommons.org/licenses/by/4.0/
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On PaperCast Base by Base you’ll discover the latest in genomics, functional genomics, structural genomics, and proteomics.
Episode link: https://basebybase.castos.com/episodes/uvb-gxe-vitamin-d-variants
Episode Slug: uvb-gxe-vitamin-d-variants
Keywords: vitamin D, gene-environment interaction, ambient UVB, GWAS, circadian rhythm

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