Background: Clinical implementation of polygenic risk scores (PRS) for precision prevention depends on the utility and barriers primary care physicians (PCPs) perceive to their use. Methods: An online survey asked PCPs in a national database about the clinical utility of PRS they perceived for categories of medical decision-making and perceived benefits of and barriers to that use. Latent class analysis (LCA) was used to identify subgroups of PCPs based on response patterns. Results: Among 367 respondents (email open rate 10.8%; participation rate 96.3%; completion rate 93.1%), mean (SD) age was 54.9 (12.9) years, 137 (37.3%) were female, and mean (SD) time since medical school graduation was 27.2 (13.3) years. Respondents reported greater perceived utility for more clinical action (e.g., earlier or more intensive screening, preventive medications, or lifestyle modification) for patients with high-risk PRS than for delayed or discontinued prevention actions for low-risk patients (p<0.001). Respondents most often chose out-of-pocket costs (48%), lack of clinical guidelines (24%), and patient insurance discrimination concerns (22%) as extreme barriers to PRS implementation. LCA identified 3 subclasses of respondents. Skeptics (n=83, 22.6%) endorsed less agreement with individual clinical utilities, saw patient anxiety and insurance discrimination as significant barriers, and agreed less often that PRS could help patients make better health decisions. Learners (n=134, 36.5%) and enthusiasts (n=150, 40.9%) expressed similar levels of agreement that PRS had utility for preventive actions and that PRS could be useful for patient decision-making. Compared with enthusiasts, however, learners perceived greater barriers to the clinical use of PRS. Conclusion: PCPs generally endorsed using PRS to guide medical decision-making about preventive care, with a preference for more clinical action over less. Barriers identified suggest interventions to address the needs and concerns of PCPs along the spectrum of acceptance and uptake.

The authors have declared no competing interest.

This work was funded by the National Human Genome Research Institute / National Institutes of Health (R35 HG010706)

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Harvard Longwood Campus Institutional Review Board gave ethical approval for this work (Protocol #20-2098).

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.

Yes

All data produced in the present study are available upon reasonable request to the authors.