This study aims to determine the relationship between lifetime trajectories of CAD risk and genome-wide polygenic score for coronary artery disease (GPSCAD), directly compare its predictive capacity to the eleven traditional risk factors, and assess its reciprocity with the Pooled Cohort Equations (PCE), which is a clinical risk estimator. Among 28,556 individuals with a median follow-up of 21 years, the genome-wide polygenic score for coronary artery disease is a powerful predictor of lifetime risk for coronary artery disease.
The GPSCAD figures further predictive data, as evaluated by the change in C-statistic from a baseline model, including sex and age, apart from the eleven traditional factors. GPSCAD in 28,556 middle-aged participants of the Cancer Study and Malmö Diet were studied, of whom 14.4% developed CAD over a median follow-up of 21 years. The minimal correlation was observed between GPSCAD and 10-year risk defined by the PCE, and the addition of GPSCAD improved the C-statistic of the PCE model by 0.026.
In conclusion, GPSCAD can differentiate individuals into diverse trajectories of clinical risk. It also improves risk discrimination better than other clinical risk scores, and allows for refined risk estimation within any given strata of risk predicted by the current clinical estimator.