The clinical utility of polygenic risk scores in genomic medicine practices: a systematic review

Abstract

Genomic medicine aims to improve health using the individual genomic data of people to inform care. While clinical utility of genomic medicine in many monogenic, Mendelian disorders is amply demonstrated, clinical utility is less evident in polygenic traits, e.g., coronary artery disease or breast cancer. Polygenic risk scores (PRS) are subsets of individual genotypes designed to capture heritability of common traits, and hence to allow the stratification of risk of the trait in a population. We systematically reviewed the PubMed database for unequivocal evidence of clinical utility of polygenic risk scores, using stringent inclusion and exclusion criteria. While we identified studies demonstrating clinical validity in conditions where medical intervention based on a PRS is likely to benefit patient outcome, we did not identify a single study demonstrating unequivocally such a benefit, i.e. clinical utility. We conclude that while the routine use of PRSs hold great promise, translational research is still needed before they should enter mainstream clinical practice.

A genetic risk score improves risk stratification for anticoagulation-related intracerebral hemorrhage

“…Although many GRS have been developed and validated in the general population to predict diseases, they still face challenges including portability and interpretability before application in routine clinical care. 34 GRS could be especially useful in high-risk populations to identify individuals with . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.…”

“…Although many GRS have been developed and validated in the general population to predict diseases, they still face challenges including portability and interpretability before application in routine clinical care. 34 GRS could be especially useful in high-risk populations to identify individuals with 12 additional high genetic risk for intervention trials. 35 Anticoagulant users are at increased ICH risk, and the additional knowledge of individual genetic ICH risk could influence clinical decision making in situations with limited evidence or equivocality of clinical parameters.…”

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

“…11 Center for Precision Psychiatry, Massachusetts General Hospital, Boston, MA, USA. 12 Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA. 13 Channing Division of Network Medicine, Boston, MA, USA.…”

“…There are several known barriers to the clinical adoption of PRS, including the current limited evidence for their clinical utility, and the known differential predictive performance of the scores in different population groups [8,9]. Despite these concerns, early evidence suggests that there may be some clinical utility to sharing PRS in the preventive health setting [10][11][12]. Because we currently have very limited information about the clinical impact of sharing PRS, evidence-based guidelines supporting the use of PRS do not yet exist.…”

Inferring disease architecture and predictive ability with LDpred2-auto

“…These methods include GCTA (h 2 , Yang et al As previously shown by Daetwyler et al (2008), h 2 and p can also be used to determine how well we can predict a phenotype from using genetic variants alone. Such genetic predictors are called polygenic scores (PGS), and are getting closer to being included as part of existing clinical risk models for diseases (Torkamani et al, 2018;Lambert et al, 2019;Kumuthini et al, 2022). LDpred2 is a widely used polygenic score method that can directly build PGS using summary statistics results from genome-wide associations studies (GWAS), making it highly applicable (Privé et al, 2020b;Pain et al, 2021;Kulm et al, 2021).…”