Patient and provider perspectives on polygenic risk scores: implications for clinical reporting and utilization

Abstract

Background Polygenic risk scores (PRS), which offer information about genomic risk for common diseases, have been proposed for clinical implementation. The ways in which PRS information may influence a patient’s health trajectory depend on how both the patient and their primary care provider (PCP) interpret and act on PRS information. We aimed to probe patient and PCP responses to PRS clinical reporting choices Methods Qualitative semi-structured interviews of both patients (N=25) and PCPs (N=21) exploring responses to mock PRS clinical reports of two different designs: binary and continuous representations of PRS. Results Many patients did not understand the numbers representing risk, with high numeracy patients being the exception. However, all the patients still understood a key takeaway that they should ask their PCP about actions to lower their disease risk. PCPs described a diverse range of heuristics they would use to interpret and act on PRS information. Three separate use cases for PRS emerged: to aid in gray-area clinical decision-making, to encourage patients to do what PCPs think patients should be doing anyway (such as exercising regularly), and to identify previously unrecognized high-risk patients. PCPs indicated that receiving “below average risk” information could be both beneficial and potentially harmful, depending on the use case. For “increased risk” patients, PCPs were favorable towards integrating PRS information into their practice, though some would only act in the presence of evidence-based guidelines. PCPs describe the report as more than a way to convey information, viewing it as something to structure the whole interaction with the patient. Both patients and PCPs preferred the continuous over the binary representation of PRS (23/25 and 17/21, respectively). We offer recommendations for the developers of PRS to consider for PRS clinical report design in the light of these patient and PCP viewpoints. Conclusions PCPs saw PRS information as a natural extension of their current practice. The most pressing gap for PRS implementation is evidence for clinical utility. Careful clinical report design can help ensure that benefits are realized and harms are minimized.

Impact of individual level uncertainty of lung cancer polygenic risk score (PRS) on risk stratification

“…A critical concern of PRS application is delivering inaccurate risk estimates at the individual level, and wrongly categorizing an individual as low or high genetic risk based on unstable PRS estimates. The downstream effect could be inappropriate or even contradictory medical advice or clinical decisions [ 25 ]. Our study shows substantial disagreement in risk categorization using different lung cancer PRSs (PRS-16, PRS-16-CV, and PRS-Bayes), suggesting that individuals that were identified as very high risk by one PRS method may not be classified as such by another.…”

“…Unfortunately, to date, the predictive accuracy of PRS has been mostly evaluated at the population level using cohort-level metrics of prediction R 2 and area under the curve (AUC), with its precision at a single individual level remaining largely unexplored [ 21 , 22 ]. Moreover, whether individual-level PRS instability would influence the subsequent clinical utilization of PRS-based risk stratification and prediction is also of great interest to discover [ 21 – 25 ]. In recent studies, the individual level uncertainty in PRS estimation on various traits including height and body mass index, and diseases including breast cancer, hypertension, and dementia have been assessed in the British population using UK Biobank data [ 21 , 22 ].…”

Recent advances in polygenic scores: translation, equitability, methods and FAIR tools

“…Over 95% of recent GWAS study participants have been of European ancestry [ 107 , 113 ]. Several recent reviews [ 5 , 114 – 116 ] have also acknowledged the transferability issue of PGS.…”

“…Polygenic risk ultimately has to be communicated to many different stakeholders, including patients (and/or consumers of commercial genetic testing) and clinicians if they are to be used in the clinic. Understanding of PGS among these groups may be low, so effective PGS reports and communication [ 150 ] are critical [ 114 , 151 ] — some examples of reports being used to communicate PGS results already exist [ 17 , 152 ]. Notably, it is important that PGS reports/results do not convey genetic determinism (that genetics predictions are fait accompli ) or exceptionalism (that genetic predisposition is more important than other risk factors).…”

Ethical layering in AI-driven polygenic risk scores—New complexities, new challenges

“…To this end, “effective and clear risk communication by trained professionals” should “minimize potential psychosocial effects” ( Adeyemo et al, 2021 ). However, in this context, there is a lack of standardised PRS disclosure for individuals ( Brockman et al, 2021 ; Lewis et al, 2022 ) as well as for kin, such as cascade screening for family members ( Reid et al, 2021 ). Tools for standardisation of PRS disclosure have been developed for certain diseases, such as coronary artery disease ( Widen et al, 2022 ), but the need for additional research on a broader range of populations and better standardisation has been emphasised ( Brockman et al, 2021 ).…”