Improved characterization of gene-environment interactions for vitamin D through variance quantitative trait loci
Bibliographic record
Abstract
Background Understanding gene-environment interaction effects influencing vitamin D status may refine nutrition and public health strategies for vitamin D deficiency. Recent methodological advances have enabled the identification of variance quantitative trait loci (vQTLs) where gene-environment interaction effects are enriched. Objectives To identify vQTLs for serum 25-hydroxy vitamin D (25OHD) concentration and characterize potential gene-environment interaction effects of vQTLs. Methods We conducted vQTL discovery for 25OHD using a newly developed quantile integral linear model in the UK Biobank individuals of European (N = 313,514), African (N = 7,800), East Asian (N = 2,146), and South Asian (N = 8,771) ancestries, respectively. We tested for interaction effects between the identified vQTL lead variants and 18 environmental, biological, or lifestyle factors, followed by multiple sensitivity analyses. Results We identified 19 independent vQTL lead variants (p-value <5x10-8) in the European ancestry population. No vQTLs were identified in the non-European ancestry populations, likely due to limited sample sizes. A total of 32 interaction effects were detected with a false discovery rate <0.05. While known gene-season of measurement interaction effects were confirmed, additional interaction effects were identified involving modifiable risk factors, including time spent outdoors and body mass index. The magnitudes of these interaction effects were consistent within each locus upon adjusting for season of measurement and other covariates. We also identified a gene-sex interaction at a vQTL that implicates DHCR7. Integrating transcript- and protein-level evidence, we found that the sex-differentiated genetic effects may act through sex-biased expression of DHCR7 isoforms in skin tissues due to alternative splicing. Conclusions Through the lens of vQTLs, we identified additional gene-environment interaction effects affecting vitamin D status apart from season of measurement. These findings may provide new insights into the etiology of vitamin D deficiency and encourage personalized prevention and management of associated diseases for at-risk individuals.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.005 | 0.009 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".