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

Abstract

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.

How Communicating Polygenic and Clinical Risk for Atherosclerotic Cardiovascular Disease Impacts Health Behavior: an Observational Follow-up Study

“…Previously, studies including a few 100 participants have reported that disclosure of PRS for coronary heart disease increases the perception of personal control, 8 information seeking, and sharing 9 and that PRS information is considered both understandable and actionable. 10 Furthermore, randomized trial of 94 individuals showed modest effects on weight loss and physical activity among participants with a higher PRS. 21 In accordance with these findings, our study further adds that receiving personal genome-based disease risk information motivates individuals at elevated disease risk more than others and show that a substantial proportion of individuals at high risk also undertake relevant actions to promote their health.…”

“…6 Nonetheless, post hoc analyses of large-scale statin trials indicate that the efficacy of statin therapy to prevent ischemic events may be higher in persons with high polygenic risk than with low polygenic risk. 7 While a few smaller-sized studies have reported that disclosure of PRS for CHD is associated with increased perception of personal control, 8 or increased information seeking and sharing, 9 and that PRS information is perceived to be both understandable and actionable, 10 it still remains unclear how delivery of polygenic risk information in a real-world setting may impact on an individual’s motivation and willingness to adopt and maintain appropriate risk reducing behavior. In particular, it remains unknown how knowing one’s personal genomic risk for ASCVD may impact on the propensity to seek care.…”

Patient and Clinician Perceptions of Precision Cardiology Care: Findings From the HeartCare Study

“…5,19,20 Our results also align with emerging evidence on patient-participants' responses to coronary artery disease PRS; among adults who had previously undergone direct-to-consumer genetic testing, receipt of a coronary artery disease PRS result was associated with uptake of risk-reducing behaviors but not with health-related anxiety. 21 Patient-participants who received positive results reported more frequently than those who received negative results that their doctor had recommended changes to their clinical care and had recommended that their family members receive genetic or other clinical testing. Given that responsibility lies with the patient to communicate clinicians' recommendations to their family members, it is crucial that patients understand whether and how their genetic testing results have implications for relatives' health.…”

“…5,19,20 Our results also align with emerging evidence on patient-participants’ responses to coronary artery disease PRS; among adults who had previously undergone direct-to-consumer genetic testing, receipt of a coronary artery disease PRS result was associated with uptake of risk-reducing behaviors but not with health-related anxiety. 21…”