Mendelian Randomization Studies Do Not Support a Role for Vitamin D in Coronary Artery Disease
Bibliographic record
Abstract
BACKGROUND: Observational studies support a possible association between decreased vitamin D levels and risk of coronary artery disease (CAD); however, it remains unclear whether this relationship is causal. We aimed to evaluate whether genetically lowered vitamin D levels influence the risk of CAD using a Mendelian randomization approach. METHODS AND RESULTS: In this 2-stage Mendelian randomization study, we first identified single-nucleotide polymorphisms associated with 25-hydroxyvitamin D (25OHD) levels in the SUNLIGHT consortium (n=33 996), then tested them for possible violation of Mendelian randomization assumptions. A count of risk alleles was tested for association with 25OHD levels in a separate cohort (n=2347). Alleles were weighted by their relative effect on 25OHD and tested for their combined effect on CAD in the Coronary Artery Disease Genome-Wide Replication and Meta-Analysis (CARDIoGRAM) study (22 233 cases/64 762 controls). Four single-nucleotide polymorphisms were identified to be associated with 25OHD levels, all in or near genes implicated in 25OHD synthesis, transport or metabolism. A count of these risk alleles was strongly associated with 25OHD (n=2347, F-test statistic=49.7, P=2×10(-12)). None of the single-nucleotide polymorphisms associated with 25OHD levels were associated with CAD (all P values >0.6). The Mendelian randomization odds ratio (OR) for CAD was 0.99 (95% confidence interval, 0.84-1.17; P=0.93; I(2)=0) per SD decrease in log-transformed 25OHD levels. These results persisted after sensitivity analyses for population stratification and pleiotropy. CONCLUSIONS: Genetically lowered 25OHD levels were not associated with increased risk of CAD in a large, well-powered study, suggesting that previous associations between circulating 25OHD levels and CAD are possibly confounded or due to reverse causation.
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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 | 0.145 | 0.309 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.007 | 0.007 |
| Bibliometrics | 0.002 | 0.004 |
| Science and technology studies | 0.001 | 0.006 |
| Scholarly communication | 0.003 | 0.003 |
| Open science | 0.004 | 0.001 |
| Research integrity | 0.005 | 0.003 |
| Insufficient payload (model declined to judge) | 0.009 | 0.001 |
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".