Return of polygenic risk scores in research: Stakeholders’ views on the eMERGE-IV study

• Published in: HGG advances 2024-04, Vol.5 (2), p.100281, Article 100281
• Main Authors: Sabatello, Maya, Bakken, Suzanne, Chung, Wendy K., Cohn, Elizabeth, Crew, Katherine D., Kiryluk, Krzysztof, Kukafka, Rita, Weng, Chunhua, Appelbaum, Paul S.
• Format: Article
• Language: English
• Subjects: barriers; chronic diseases; equity; Institutional Review Board; IRB; polygenic risk scores, PRS; return of results; translational genomic efforts
• ISSN: 2666-2477; 2666-2477
• DOI: 10.1016/j.xhgg.2024.100281

Research on polygenic risk scores (PRSs) for common, genetically complex chronic diseases aims to improve health-related predictions, tailor risk-reducing interventions, and improve health outcomes. Yet, the study and use of PRSs in clinical settings raise equity, clinical, and regulatory challenges that can be greater for individuals from historically marginalized racial, ethnic, and other minoritized communities. As part of the National Human Genome Research Institute-funded Electronic Medical Records and Genomics IV Network, we conducted online focus groups with patients/community members, clinicians, and members of institutional review boards to explore their views on key issues, including PRS research, return of PRS results, clinical translation, and barriers and facilitators to health behavioral changes in response to PRS results. Across stakeholder groups, our findings indicate support for PRS development and a strong interest in having PRS results returned to research participants. However, we also found multi-level barriers and significant differences in stakeholders’ views about what is needed and possible for successful implementation. These include researcher-participant interaction formats, health and genomic literacy, and a range of structural barriers, such as financial instability, insurance coverage, and the absence of health-supporting infrastructure and affordable healthy food options in poorer neighborhoods. Our findings highlight the need to revisit and implement measures in PRS studies (e.g., incentives and resources for follow-up care), as well as system-level policies to promote equity in genomic research and health outcomes. A focus groups study with patients, community members, clinicians, and members of IRBs found support for the development of PRSs and interest in having PRS results returned to research participants but also multi-level barriers and significant differences in stakeholders’ views about what is needed and possible for successful implementation.