Response to Polygenic Risk: Results of the MyGeneRank Mobile Application-Based Coronary Artery Disease Study

Muse, E. D.; Chen, S.; Liu, S.; Fernandez, B.; Schrader, B.; Molparia, B.; Leon, A. N.; Lee, R.; Pubbi, N.; Mejia, N.; Ren, C.; El-kalliny, A.; Montes de Oca, E. P.; Aguilar-Fraga, H. O.; Ghoshal, A.; Dias, R.; Evans, D.; Chen, K.-Y.; Zhang, P.; Wineinger, N. E.; Spencer, E.; Topol, E. J.; Torkamani, A.

The degree to which polygenic risk scores (PRS) influence preventive health is the subject of debate, with few prospective studies completed to date. We developed a smartphone application for the prospective and automated generation, communication, and electronic capture of response to a PRS for coronary artery disease (CAD). We evaluated self-reported actions taken in response to personal CAD PRS information, with special interest in the initiation of lipid lowering therapy (NCT03277365). 20% of high genetic risk (n=95) vs 7.9% of low genetic risk individuals (n=101) initiated lipid lowering therapy at follow-up (p-value = 0.002). The initiation of both statin and non-statin lipid lowering therapy was associated with degree of genetic risk: 15.2% (n=92) vs 6.0% (n=100) for statins (p-value = 0.018) and 6.8% (n=118) vs 1.6% (n=123) for non-statins (p-value = 0.022) in high vs low genetic risk, respectively. Overall, degree of genetic risk was associated with use of any lipid lowering therapy at follow-up: 42.4% (n=132) vs 28.5% (n=130) (p-value = 0.009). We also find that CAD PRS information is perceived to be understandable, actionable, and does not induce health anxiety.