Polygenic risk scores in the clinic: a systematic review of stakeholders' perspectives, attitudes, and experiences.

Polygenic Risk Scores (PRS) are statistical methods estimating part of an individual's genetic susceptibility to various disease phenotypes. Their potential clinical applications to enhance the prediction, prevention, and risk management of complex conditions motivate current research efforts worldwide. While a growing body of literature has highlighted the scientific and ethical limitations of PRS, the technology's clinical translation will present both opportunities and challenges for the stakeholders involved. Here, a mixed-method systematic review of empirical studies was performed to gather evidence on the perspectives, attitudes, and experiences of healthcare providers, patients, and the public regarding the use of PRS in healthcare settings. The PRISMA reporting protocol was followed and 24 articles were included. Three major themes were identified. First, we reported on participants' familiarity with the test, including their knowledge, understanding, and education on PRS' clinical use. The second theme collects stakeholders' motivations for taking the test and their perspectives on sensitive issues related to the return of results. Participants' normative stances regarding the appropriate use of PRS, their benefits, and harms were presented in the third theme. The findings underscore significant knowledge gaps and challenges in the clinical interpretation of PRS among healthcare providers. On the other hand, the provision of genetic counseling benefitted patients' understanding of PRS results and in most cases, no psychosocial burden was reported. Finally, the review highlights that stakeholders' perspectives on the clinical use of PRS are highly context-dependent, shaped by population characteristics, disease type, and social factors, emphasizing the need for tailored approaches across diverse healthcare settings.