Abstract 1436: Gene Dosage of the Common Variant 9p21 Predicts Severity of Coronary Atheromatous Burden
Bibliographic record
Abstract
Background: The first common genetic risk variant for coronary artery disease (CAD), 9p21, was recently identified and shown to occur in 75% of Caucasian and Asian populations. However, 9p21 does not contain a protein coding gene and its function is unknown. Given the phenotypes of atherosclerosis and thrombosis, pursuit of the molecular mechanisms mediating 9p21 risk requires elucidation of the 9p21 phenotype. Accordingly, we tested the hypothesis that 9p21 is directly related to coronary atherosclerosis. Methods: We studied 709 patients who were prospectively enrolled from the coronary catheterization laboratory at the University of Ottawa Heart institute from April 15 th 2006 to 4 th January 2008. Each subject was genotyped for the single nucleotide polymorphism rs1333049 (risk allele located at 9p21). Patients were designated AA (risk/risk), AB (risk/non-risk) and BB (non-risk/non-risk). Angiograms were reviewed by two independent parties blinded to genotype. Lesions with 50% or more stenosis were considered significant for the purposes of this study. Odds ratios were generated for proportion of patients with 3VD, significant left main disease and CABG relative to the non-risk genotype, BB. Results: We demonstrated a strong direct association between 9p21 gene dosage and 3VD (Fig. 1A ). Conversely, a strong inverse association between 9p21 gene dosage and 1VD was observed (Fig. 1B ). A strong direct association between gene dosage and LM disease (Fig. 1C ) and CABG (Fig. 1D ) was seen. Conclusions: The 9p21 variant risk is mediated through deposition of coronary atheroma. Therefore, elucidating 9p21 function should target atherogenesis.
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.007 | 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".