It’s rare that one gene causes CVD, just as it’s rare for one CV condition to occur in isolation. In a recent JACC issue, researchers show that those facts can be leveraged to improve risk assessments with a new eight-condition polygenic risk score (PRS).
- Genetics account for up to 50% of the differences in who develops CVD.
- While multi-gene risk scores usually analyze a single condition, up to two-thirds of CVD types overlap in their genetic causes.
That’s why genetic testing can reveal hidden high-risk groups often missed by traditional risk factors, and also why a polygenic risk report could multiply the benefits of standalone tests.
Enter Harvard and MIT’s researchers: Using genetic data and clinical outcomes from 245k participants, they developed and trained a tool that integrated the UK-based PGS Catalog PRS guidelines from across eight conditions:
- CAD
- AFib
- T2D
- Venous thromboembolism
- Thoracic aortic aneurysm
- Hypertension
- Hypercholesterolemia
- Elevated lipoprotein(a)
The combined PRS tool excelled when tested on 53k Mass General Brigham Biobank participants. Compared to those with average genetic risk, participants in the highest risk group (top 10%) showed…
- A 41-fold increase in the odds of elevated lipoprotein(a).
- Those patients also had 4.1x higher odds of developing hypercholesterolemia and 3.7x higher odds of developing CAD.
- The PRS predictions proved accurate – after seven years, high PRS score patients had a 2.1x higher rate of CAD and a 2.3x higher risk of AFib.
The model was better than or equal to all individual genetic-risk scoring methods at predicting future outcomes, but that’s not all. The scores also resulted in improvements in risk classification.
- Incorporating the eight-condition PRS score into PCE and PREVENT risk assessments bettered CAD-risk reclassifications by 17% and 18%, respectively.
Better risk assessments = better interventions = better outcomes, which could mean lower costs for patients and health systems. Plus, the researchers already laid out a clear workflow: Clinicians place orders, patients give saliva samples, and, six weeks later, an EHR-integrated report is uploaded.
- These genetic tests can make risk-assessments more accurate earlier in life.
- The sooner high PRS score patients implement risk-informed interventions, the better their chance of deterring disease.
While PRS may be promising, a lack of diverse studies and disagreement on PRS benchmarks may delay clinical integration.
The Takeaway
This study puts the power of PRS on full-display, showing how a combined condition multi-gene test improved CVD risk classification while not overwhelming clinical workflows. Since genetic factors underlie so much of CVD’s long-term development, integrating genetics into cardiology has the potential to bring big benefits.
