Clinical Implementation of Combined Monogenic and Polygenic Risk Disclosure for Coronary Artery Disease

JACC Adv. 2022 Aug;1(3):100068. doi: 10.1016/j.jacadv.2022.100068. Epub 2022 Aug 16.


Background: State-of-the-art genetic risk interpretation for a common complex disease such as coronary artery disease (CAD) requires assessment for both monogenic variants-such as those related to familial hypercholesterolemia-as well as the cumulative impact of many common variants, as quantified by a polygenic score.

Objectives: The objective of the study was to describe a combined monogenic and polygenic CAD risk assessment program and examine its impact on patient understanding and changes to clinical management.

Methods: Study participants attended an initial visit in a preventive genomics clinic and a disclosure visit to discuss results and recommendations, primarily via telemedicine. Digital postdisclosure surveys and chart review evaluated the impact of disclosure.

Results: There were 60 participants (mean age 51 years, 37% women, 72% with no known CAD), including 30 (50%) referred by their cardiologists and 30 (50%) self-referred. Two (3%) participants had a monogenic variant pathogenic for familial hypercholesterolemia, and 19 (32%) had a high polygenic score in the top quintile of the population distribution. In a postdisclosure survey, both the genetic test report (in 80% of participants) and the discussion with the clinician (in 89% of participants) were ranked as very or extremely helpful in understanding the result. Of the 42 participants without CAD, 17 or 40% had a change in management, including statin initiation, statin intensification, or coronary imaging.

Conclusions: Combined monogenic and polygenic assessments for CAD risk provided by preventive genomics clinics are beneficial for patients and result in changes in management in a significant portion of patients.

Keywords: coronary artery disease; genetics; genomic medicine; polygenic score; precision medicine; preventive cardiology.