Clinical Application of Polygenic Risk Scores Statement

This document is a statement from the American College of Medical Genetics and Genomics (ACMG) regarding the clinical application of polygenic risk scores (PRS). It outlines the nature of polygenic inheritance and the role of PRS in predicting the risk of various complex disorders. The statement emphasizes that PRS is derived from genome-wide association studies (GWAS) and provides a statistical prediction of disease risk rather than a definitive diagnosis. It discusses the limitations of PRS, particularly concerning the historical reliance on European genetic data, which may hinder its applicability to diverse populations. The document also addresses the absence of clinical guidelines for PRS use and encourages clinicians to consider individual patient contexts when interpreting PRS results. Furthermore, it highlights the need for prospective studies to evaluate the clinical utility of PRS in guiding medical management. Overall, the ACMG aims to provide guidance on the challenges and considerations in applying PRS testing in clinical practice.