Clinical Implementation of Combined Monogenic and Polygenic Risk Disclosure for Coronary Artery Disease
Dimitri J Maamari1,2,3, Deanna G Brockman1,2, Krishna Aragam2,4,5
1Center for Genomic Medicine, Department of Internal Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Insights
A new genetic risk assessment combining monogenic and polygenic scores for coronary artery disease (CAD) improved patient understanding and led to significant changes in clinical management for many participants.
Area of Science:
- Genomics and Precision Medicine
- Cardiovascular Disease Research
- Preventive Healthcare
Background:
- Coronary artery disease (CAD) risk assessment requires evaluating both rare, high-impact monogenic variants (e.g., familial hypercholesterolemia) and common polygenic variants.
- Integrating these genetic factors provides a more comprehensive understanding of an individual's predisposition to CAD.
Purpose of the Study:
- To describe a novel program combining monogenic and polygenic risk assessment for CAD.
- To evaluate the program's impact on patient comprehension of their genetic risk.
- To determine if the assessment influences clinical management decisions.
Main Methods:
- Sixty participants attended a preventive genomics clinic for combined genetic risk assessment.
- Assessments were followed by telemedicine-based disclosure visits.
- Patient understanding and changes in clinical management were evaluated via digital surveys and chart reviews.
Main Results:
- Two participants (3%) had pathogenic monogenic variants for familial hypercholesterolemia; 19 (32%) had a high polygenic risk score.
- 89% found the clinician discussion helpful for understanding results.
- 40% of participants without prior CAD experienced a management change (e.g., statin initiation/intensification, coronary imaging).
Conclusions:
- Combined genetic risk assessment for CAD in a preventive genomics setting is effective.
- This approach enhances patient understanding and leads to actionable changes in clinical practice.
- The findings support the integration of comprehensive genetic risk profiling into cardiovascular care.
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.
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