Graduate Research Assistant University of Washington, United States
Polygenic risk scores (PRS), which provide estimates of disease risk by aggregating the effects of thousands of common variants across the genome, have been proposed as an important new tool for precision medicine. However, many PRS currently underperform in patients from populations underrepresented in genome-wide association studies, and these ancestry-based limitations could pose a barrier to ethical clinical implementation. Research on primary care providers' (PCPs’) perceptions of the clinical utility of PRS for non-European-descended patients is lacking.
We conducted semi-structured interviews with 20 PCPs. After eliciting general views about PRS, we presented hypothetical scenarios designed to explore clinical reasoning and decision-making in the face of possible test outcomes. Scenarios varied with regard to whether the tested patient was symptomatic; asymptomatic and previously assessed as low-risk by other measures; or from a population background for which PRS were more uncertain. We varied the order of scenarios among interviews to minimize framing effects. Participants’ views on ancestry-based limitations of PRS varied. PCPs expressed concerns about health equity implications and potential negative repercussions for the therapeutic alliance. In response to the scenarios, most PCPs said they would treat PRS cautiously, and would seldom consider PRS dispositive; they would consider results in the context of other relevant information. There was some evidence to suggest that race-based risk heuristics would be favored when PRS results were uncertain. Findings underscore the need for additional research to increase the population relevance of PRS, as well as the development of clinical guidance and decision support for PCPs.
