Transferability, Calibration, and Decision Thresholds of Polygenic Risk Scores for Coronary Artery Disease in Latinx Populations: Bench-To-Population Perspectives

Kirenyo Nalubega F.

Faculty of Medicine Kampala International University Uganda

ABSTRACT

Polygenic risk scores (PRSs) for coronary artery disease (CAD) hold promise for improving early risk stratification and preventive cardiology, yet their clinical translation across diverse populations remains challenging. This paper examines the transferability, calibration, and clinical decision thresholds of CAD PRSs in Latinx populations from a bench-to-population perspective. It synthesizes current evidence on how differences in genetic ancestry, linkage disequilibrium structure, allele frequencies, and environmental context influence predictive performance when PRSs derived largely from European genome-wide association studies are applied to Latinx cohorts. The analysis highlights that while some multi-ancestry models retain a partial predictive signal, performance often declines, with systematic miscalibration leading to over- or underestimation of absolute risk. Recalibration methods, including adjustment of intercepts and slopes and incorporation of population-specific prevalence data, can improve clinical reliability. Determining appropriate decision thresholds is also critical, as differences in disease prevalence and baseline risk necessitate ancestry-informed cut-points to balance sensitivity and specificity in screening and prevention strategies. The paper further discusses methodological, ethical, and implementation considerations, including dataset representation, governance of genomic data, and integration with traditional cardiovascular risk assessment tools. Strengthening Latinx representation in genomic research and developing ancestry-aware modelling strategies are essential to ensure equitable clinical utility. Ultimately, optimizing PRS transferability, calibration, and threshold selection could enable more accurate and inclusive genomic risk prediction for CAD in Latinx populations.

Keywords: Polygenic risk scores, Coronary artery disease, Latinx populations, Genetic risk prediction, Calibration and transferability

CITE AS: Kirenyo Nalubega F. (2026). Transferability, Calibration, and Decision Thresholds of Polygenic Risk Scores for Coronary Artery Disease in Latinx Populations: Bench-To-Population Perspectives. RESEARCH INVENTION JOURNAL OF PUBLIC HEALTH AND PHARMACY 5(1): 117-122. https://doi.org/10.59298/RIJPP/2026/51117122