Polygenic risk score refines cardiovascular disease risk in individuals with type 2 diabetes at borderline or intermediate risk

ABSTRACT To evaluate whether a coronary artery disease (CAD) polygenic risk score (PRS) can improve atherosclerotic cardiovascular disease (ASCVD) risk stratification in individuals with type 2 diabetes (T2D), particularly those at borderline or intermediate 10‐year risk. In the UK Biobank ( n = 340,299), we integrated CAD PRS into the Pooled Cohort Equations (PCE) to evaluate whether it improved the prediction of incident ASCVD in individuals with T2D at borderline and intermediate 10‐year risk. CAD PRS was associated with ASCVD in T2D (1.18‐fold). Among those at borderline and intermediate risk, PRS was strongly predictive (1.47‐fold and 1.11‐fold), and individuals in the top 10% had 1.86‐fold and 1.32‐fold higher risk. Integration of PRS into PCE modestly improved AUROC (0.050, P = 0.024) and significantly improved net reclassification (0.343, P = 2.62 × 10 −4 ). CAD PRS enhances ASCVD risk prediction in individuals with T2D, supporting utilizing genetic information in tailored risk stratification and preventive care.