Clinical Utility and Practical Considerations of a Coronary Artery Disease Genetic Risk Score
Bibliographic record
Abstract
Background Coronary artery disease (CAD) risk traditionally has been assessed using clinical risk factors. We evaluated whether molecular genetic markers for CAD risk could add information to traditional variables. Methods We developed a false discovery rate 267-marker genetic risk score (FDR 267 ) from markers that were significantly associated with CAD in the UK Biobank cohort meta-analysis. FDR 267 was tested in the Atherosclerosis Risk in Communities cohort using logistic regression and Cox proportional hazards analyses in the European and African American groups. Results Our genetic risk score (FDR 267 ) was associated with a 1.45 (95% confidence interval, 1.39-1.51) increase in odds ratio and a 1.32 (95% confidence interval, 1.26-1.38) increase in hazard ratio per standard deviation of the score. The score modestly improved the area under the curve (AUC) statistic when added to a clinical model (ΔAUC = 0.0112, P = 0.0002). FDR 267 predicted incident CAD (C-index = 0.60), although it did not improve on clinical risk factors (ΔAUC = 0.0159, P = 0.0965). Individuals in the top quintile of FDR 267 genetic risk were at approximately 2-fold increased risk compared with the bottom quintile, which is comparable to risk associated with self-reported family history. The performance of FDR 267 was less robust in the African American sample. Conclusions FDR 267 is significantly associated with CAD in the European sample, with an effect size comparable to self-reported family history. FDR 267 discriminated between individuals with and without CAD, but did not improve CAD risk prediction over clinical variables. FDR 267 was less predictive of CAD risk in African Americans.
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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 | 0.099 | 0.295 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.004 | 0.003 |
| Science and technology studies | 0.000 | 0.004 |
| Scholarly communication | 0.005 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.003 | 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".