Key result
CAD PRS improves net ASCVD risk reclassification ~34% in borderline-to-intermediate T2D patients.
Why the study?
To evaluate whether a CAD polygenic risk score can improve ASCVD risk stratification in individuals with T2D, particularly those at borderline or intermediate 10-year risk.
Does integrating a CAD polygenic risk score into the Pooled Cohort Equations improve the prediction of incident ASCVD in individuals with type 2 diabetes at borderline or intermediate 10-year risk?
Does integrating a CAD polygenic risk score into the Pooled Cohort Equations improve the prediction of incident ASCVD in individuals with type 2 diabetes at borderline or intermediate 10-year risk?
Integrating a CAD polygenic risk score into standard risk equations significantly improves ASCVD risk prediction and reclassification in patients with type 2 diabetes at borderline or intermediate risk.
May improve prevention targeting in intermediate-risk type 2 diabetes; extends CAD PRS evidence but should not yet change practice.
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.
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Choi et al. (2026) studied this question. A coronary artery disease polygenic risk score significantly improved net reclassification (0.343) of cardiovascular risk in type 2 diabetes patients at borderline or intermediate risk.
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