Summary
This study presents GPS_Mult, an improved multi-ancestry polygenic risk score for coronary artery disease developed from genome-wide association data across five ancestries (>269,000 cases, >1,178,000 controls) integrated with ten CAD risk factors. The score demonstrated strong associations with both existing and future CAD events in UK Biobank participants and showed superior performance across multiethnic external validation cohorts, providing a framework for ancestry-inclusive genetic risk prediction that could improve clinical identification of high-risk individuals before disease onset.
Regional applicability
The study was directly conducted using UK Biobank participants and therefore has direct applicability to UK cardiovascular risk assessment and prevention strategies. The polygenic score could support stratified risk-based approaches to primary prevention in the UK healthcare system, though implementation would require integration with existing clinical guidelines and consideration of health equity across diverse UK populations.
Key measures
Odds ratio per standard deviation for prevalent CAD (2.14); hazard ratio per standard deviation for incident CAD (1.73); risk stratification by quintile; external validation across African, European, Hispanic, and South Asian ancestry cohorts
Outcomes reported
The study measured associations between GPS_Mult polygenic risk scores and both prevalent and incident coronary artery disease across diverse ancestry populations. GPS_Mult identified individuals at substantially elevated or reduced CAD risk and demonstrated superior predictive performance compared to previously published polygenic scores.
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