March 2, 2021Circulation Genomic and Precision MedicineOpen Access

Integrated Polygenic Tool Substantially Enhances Coronary Artery Disease Prediction

Q: What are the key findings of this study?

An integrated risk tool combining a polygenic risk score with pooled cohort equations yielded an overall net reclassification improvement of 5.9% for incident coronary artery disease compared to pooled cohort equations alone.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Coronary Artery Disease (n=186451). Intervention: Integrated risk tool (IRT) combining polygenic risk score (PRS) with pooled cohort equations (PCE) vs. Pooled cohort equations (PCE) alone. Primary outcome: Net reclassification improvement (NRI) for incident CAD (NRI 5.9%, 95% CI 4.7-7.0, p=<0.005).

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Key result

Adding a polygenic risk score to pooled cohort equations improves incident CAD risk reclassification by ~6%.

NRI 5.9%
95% CI 4.7-7.0
P<0.005
n=186,451

Why the study?

Cardiovascular disease risk calculators are routinely used to guide preventive treatment, but whether incorporating genetic data can improve these standard tools remained an open question.

Does an integrated risk tool combining a polygenic risk score with established clinical calculators improve predictive accuracy for coronary artery disease events in the general population?

Population

60 000 individuals for development and 186 451 independent individuals for testing in the UK Biobank

Comparison

Integrated risk tool combining polygenic risk score with PCE or QRISK3 vs established risk tools alone

Design

Risk tool development and validation study in a prospective cohort

Authors

FRFernando Riveros-MckayGenomics (United Kingdom)MWMichael E. WealeGenomics England RMRachel MooreSt Louis Community College

Discussion

Member takes

Implication

May modestly improve CAD reclassification in cohorts; leaves open prospective validation before clinical adoption.

Study Design

Type

Cohort (n=186,451)

Multicenter

Yes

Structured PICO

Does an integrated risk tool combining a polygenic risk score with established clinical calculators improve predictive accuracy for coronary artery disease events in the general population?

Population

246,451 UK Biobank individuals (60,000 for development of the integrated risk tool, 186,451 for independent testing)

Intervention

Integrated risk tool (IRT) combining a novel coronary artery disease polygenic risk score with established risk tools (PCE or QRISK3)

Comparator

Established risk tools alone (PCE or QRISK3)

Outcome

Predictive accuracy and net reclassification improvement for incident coronary artery disease eventssurrogate

Main Result

Effect estimate: NRI 5.9% (95% CI 4.7-7.0)

p-value: p=<0.005

An integrated risk tool combining polygenic risk scores with standard clinical calculators significantly improves coronary artery disease risk stratification and reclassification.

Limitations

Cohort is of primarily European ancestries
Age range of participants at UKB assessment is limited to 40 to 69 years
Participants tend to be healthier and more affluent than the general UK population
Assessment of a simple single-risk-assessment-at-baseline scenario rather than a continuous-assessment scenario
Blanket exclusion of samples with missing data
PRS is constructed from common variants without rare high-risk variants
Evaluation of PCE and QRISK3 risk tools only
Reliance on UKB data that included self-report to define some outcomes
Use of prevalent CAD cases in the construction of the PRS
Single PRS applied uniformly to all individuals regardless of age, sex, or other factors

Cite This Study

Riveros-Mckay et al. (2021) conducted a cohort in Coronary Artery Disease (n=186,451). Integrated risk tool (IRT) combining polygenic risk score (PRS) with pooled cohort equations (PCE) vs. Pooled cohort equations (PCE) alone was evaluated on Net reclassification improvement (NRI) for incident CAD (NRI 5.9%, 95% CI 4.7-7.0, p=<0.005). An integrated risk tool combining a polygenic risk score with pooled cohort equations yielded an overall net reclassification improvement of 5.9% for incident coronary artery disease compared to pooled cohort equations alone.

synapsesocial.com/papers/6a11e4a671528255b221bd59 https://doi.org/10.1161/circgen.120.003304

Topics

Coronary artery disease

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Integrated Polygenic Tool Substantially Enhances Coronary Artery Disease Prediction

Discussion

Member takes

Implication

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Topics

Integrated Polygenic Tool Substantially Enhances Coronary Artery Disease Prediction

Discussion

Member takes

Implication

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Topics

Also Consider