SMART-Topic: Polygenic Risk Score (PRS): Development, Interpretation and Utility

Polygenic Risk Scores (PRS) use dozens to hundreds of genetic variants from disease populations to add insights to an individual’s risk of that disease. Many PRSs are undergoing clinical trials to assess their ability to enhance clinical risk assessments, making the assessments more personal and accurate while enabling earlier implementation of disease mitigation strategies.(3-7) This paper focuses on the development, utility, interpretation, and limitations of PRS in clinical practice. A PRS is the weighted sum of disease risk contributed by multiple, common, single nucleotide variants (SNVs) across the genome. PRSs are developed using output from one or more genome-wide association studies (GWAS) and are effective for both binary and continuous traits. The accuracy and utility of a PRS depend on the SNVs used in the GWAS, the selection of SNVs for the PRS, the population tested, the characteristics of the disorder, and the accuracy of phenotyping. Interpretation must be done in the context of overall patient risk, such as age, sex, ancestry, past medical history, family history, lifestyle, and biomarkers. Better tools are needed for translation of PRS into the clinical practice of healthcare professionals