Polygenic risk scores in predicting the presence of coronary artery disease in symptomatic patients - A validation study utilizing an accurate phenotype based on state-of-the-art imaging

Abstract

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Academy of Finland Turku University Hospital. Background Clinical risk scores for coronary artery disease (CAD) are used routinely in clinical practice to identify high risk patients in which diagnostic testing and therapy are warranted. Several recent studies suggested that polygenic risk scores (PRS) derived from millions genetic variants and hundreds of thousands subjects are able to identify those with higher risk of developing CAD. PRSs have been proposed to be included in clinical care, but their performance in clinical setting has not been validated. Purpose Our aim was to assess the predictive power of 4 established PRSs in prediction of CAD. Methods The study was carried out in 943 symptomatic patients with suspected CAD for whom the phenotype has been accurately characterized using state-of-the-art anatomic (CTA) and functional imaging (PET perfusion). Results The ROC curves for models combining clinical data and PRS in predicting obstructive CAD are shown in Figure. The predictive accuracy of the models combining clinical data and different PRS varied between 0.778–0.805 (in terms of AUROC), being close to the model including only clinical variables (AUROC 0.769) and yielding an improvement of only 0.9–3.6 percentage points over clinical data alone. The difference between clinical model and combined clinical + PRS model was not significant for PRS1 (p = 0.479), PRS2 (p = 0.627) and PRS4 (p = 0.061), respectively. Only PRS3 slightly (AUC change 0.036) but nominally significantly improved the predictive power of the model (p = 0.04). Conclusions We found that the addition of PRSs to conventional risk factors did not clinically significantly improve the predictive accuracy for either coronary atherosclerosis or obstructive CAD, suggesting that current PRSs are not justified for clinical routine for CAD.