2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Characterizing clinical actionability in the context of polygenic risk assessment

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The ClinGen Actionability Working Group is adapting an existing framework for assessing the clinical actionability of genetic findings to the context of polygenic risk assessment. The framework is being developed to improve health outcomes by targeting medical interventions more accurately through the use of polygenic risk scores (PRS). The existing framework for monogenic conditions involves curation of evidence, scoring of four actionability domains, and generating an actionability assertion. This framework will be extended to PRS actionability with the development of curation and scoring protocols.<br /><br />Considerations for adapting the framework to the polygenic context include the impact of PRS on a population scale, the ability to detect and screen for conditions, evaluation across ancestral populations, and the cost effectiveness of interventions. The severity and likelihood of the outcome, effectiveness of the intervention, nature of the intervention, and level of evidence are factors that will be taken into account when scoring the actionability domains.<br /><br />The ClinGen AWG plans to pilot test the framework using breast cancer and coronary heart disease as exemplar conditions. Feedback from interested parties and the results of the pilot testing will inform future refinements of the framework. The goal of this work is to provide resources for decision-making regarding the implementation of PRS into clinical care based on evidence of clinical actionability.<br /><br />The research is supported by grants from the National Human Genome Research Institute of the National Institutes of Health.

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Presenting Author - Bradford C. Powell, MD, PhD, FACMG; Co-Author - Adam H. Buchanan, MS, MPH, CGC; Co-Author - Joanna Bulkley, PhD; Co-Author - Montserrat Garcia-Closas, MD, Dr.P.H; Co-Author - Katrina AB. Goddard, PhD; Co-Author - Stefan Massimino, MS; Co-Author - Iftikhar J. Kullo, MD; Co-Author - Jessica E. Hunter, PhD;

Meta Tag

Ethical Legal and Social Issues

Polygenic risk scores

Population Genetics

Risk Assessment

Co-Author Adam H. Buchanan, MS, MPH, CGC

Co-Author Joanna Bulkley, PhD

Co-Author Montserrat Garcia-Closas, MD, Dr.P.H

Co-Author Katrina AB. Goddard, PhD

Co-Author Stefan Massimino, MS

Co-Author Iftikhar J. Kullo, MD

Co-Author Jessica E. Hunter, PhD

Presenting Author Bradford C. Powell, MD, PhD, FACMG

Keywords

polygenic risk assessment

medical interventions

actionability domains

PRS actionability

ancestral populations

cost effectiveness

breast cancer

coronary heart disease

clinical care

evidence