Polygenic Risk Scores for Personalized Cardiovascular Pharmacogenomics―A Scoping Review
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
Cardiovascular disease (CVD) is the leading cause of mortality worldwide, often involving a strong genetic background. Polygenic risk scores (PRSs) combine the cumulative effects of multiple genetic variants to quantify an individual’s susceptibility to CVD. Pharmacogenomics (PGx) can further personalize treatment by tailoring medication choices to an individual’s genetic profile. Even with these potential benefits, the extent to which PRS can be integrated into the PGx of CVD remains unclear. Our review provides an overview of current evidence on the application of PRS in the PGx of CVD, examining clinical utility and limitations and providing directions for future research. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews protocol, we conducted a comprehensive literature search in PubMed, EMBASE, and the Web of Science. Studies investigating the relationship between PRS in predicting the efficacy, adverse effects, or cost-effectiveness of cardiovascular medications were selected. Of the 1894 articles identified, 32 met the inclusion criteria. These studies predominantly examined lipid-lowering therapies, antihypertensives, and antiplatelets, although other medication classes (e.g., rate-control drugs, ibuprofen/acetaminophen, diuretics, and antiarrhythmics) were also included. Our findings showed that PRS is most robustly validated in lipid-lowering therapies, especially statins, where studies reported that individuals with higher PRSs derived the greatest reduction in lipids while on statins. Studies analyzing antihypertensives, antiplatelets, and antiarrhythmic medications demonstrated more variable outcomes, though certain PRSs did identify subgroups with significantly improved response rates or a higher risk of adverse events. Though PRS was a strong tool in many cases, we found some key limitations in its applicability in research, such as the under-representation of non-European-ancestry cohorts in the examined studies and a lack of standardized outcome reporting. In conclusion, though PRS offers promise in improving the efficacy of PGx of CVD by enhancing the personalization of medication on an individual level, several obstacles, such as the need for including a broader ancestral diversity and more robust cost-effectiveness data remain. Future research must (i) prioritize validating PRS in ethnically diverse populations, (ii) refine PRS derivation methods to tailor them for drug response phenotypes, and (iii) establish clear and attainable guidelines for standardizing the reporting of outcomes.
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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 | 0.006 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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