243: Genome-wide UVB GxE study finds 162 vitamin D variants

Shraim R et al., Nat Commun - 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. Key terms: vitamin D, gene-environment interaction, ambient UVB, GWAS, circadian rhythm.

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:
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First author:
Shraim R

Journal:
Nat Commun

DOI:
10.1038/s41467-025-65820-x

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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QC:
This episode was checked against the original article PDF and publication metadata for the episode release published on 2025-12-29.

QC Scope:
- article metadata and core scientific claims from the narration
- excludes analogies, intro/outro, and music
- transcript coverage: Audited the transcript's coverage of: (i) construction of the CW-D-UVB exposure metric and study scale; (ii) genome-wide and interaction results for 25OHD; (iii) heritability gradient with UVB; (iv) key genes and pathways (circadian clock, UGT glucuronidation, lipid metabolism); (v) replication across European UKB, LUR
- transcript topics: CW-D-UVB environmental exposure measurement; GWAS results for 25OHD (marginal, interaction, joint tests); Gene-environment interactions with UVB; SNP-based heritability gradient across UVB quintiles; Circadian clock genes BMAL1/ARNTL and NPAS2; UGT glucuronidation and lipid metabolism pathways

QC Summary:
- factual score: 10/10
- metadata score: 10/10
- supported core claims: 8
- claims flagged for review: 0
- metadata checks passed: 4
- metadata issues found: 0

Metadata Audited:
- article_doi
- article_title
- article_journal
- license

Factual Items Audited:
- CW-D-UVB: cumulative, weighted ambient UVB dose over 135 days prior to sampling
- Cohort: 338,977 UK Biobank participants of White British ancestry
- Identified 307 independent 25OHD variants; 162 novel variants
- SNP-based heritability (h2SNP) increases with ambient UVB: 8.48% in CW-D-UVB Q1 vs 15.56% in Q5; outdoors ≥3h: 11.01%
- 20 variants show GxE interaction with UVB exposure; novel interaction at COPB1 and PSMA1; circadian clock genes BMAL1/ARNTL and NPAS2 implicated
- Functional annotation: enrichment in lipid metabolism pathways and glucuronidation; liver-tissue enrichment

QC result: Pass.