Exploring the Genetic Architecture of Circulating 25‐Hydroxyvitamin D
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
The primary circulating form of vitamin D is 25-hydroxy vitamin D (25(OH)D), a modifiable trait linked with a growing number of chronic diseases. In addition to environmental determinants of 25(OH)D, including dietary sources and skin ultraviolet B (UVB) exposure, twin- and family-based studies suggest that genetics contribute substantially to vitamin D variability with heritability estimates ranging from 43% to 80%. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) located in four gene regions associated with 25(OH)D. These SNPs collectively explain only a fraction of the heritability in 25(OH)D estimated by twin- and family-based studies. Using 25(OH)D concentrations and GWAS data on 5,575 subjects drawn from five cohorts, we hypothesized that genome-wide data, in the form of (1) a polygenic score comprised of hundreds or thousands of SNPs that do not individually reach GWAS significance, or (2) a linear mixed model for genome-wide complex trait analysis, would explain variance in measured circulating 25(OH)D beyond that explained by known genome-wide significant 25(OH)D-associated SNPs. GWAS identified SNPs explained 5.2% of the variation in circulating 25(OH)D in these samples and there was little evidence additional markers significantly improved predictive ability. On average, a polygenic score comprised of GWAS-identified SNPs explained a larger proportion of variation in circulating 25(OH)D than scores comprised of thousands of SNPs that were on average, nonsignificant. Employing a linear mixed model for genome-wide complex trait analysis explained little additional variability (range 0-22%). The absence of a significant polygenic effect in this relatively large sample suggests an oligogenetic architecture for 25(OH)D.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it