Polygenic risk score: a useful clinical instrument for disease prediction and risk categorization

Abstract

Genetic information is one of the essential components of precision medicine. Over the past decade, substantial progress has been made, such as low-cost, high-throughput genotyping arrays, advances in statistical techniques, and progressively larger discovery datasets, enabling the discovery of alleles contributing to common diseases, such as coronary artery disease and type 2 diabetes. The polygenic risk score (PRS) represents the aggregate contribution of numerous common genetic variants, individually conferring small to moderate effects, and can be used as a marker of genetic risk for major chronic diseases. PRSs can be obtained from early childhood, and only one measurement is needed to determine the score. PRSs can potentially be used for triage of further investigations to confirm disease susceptibility and to optimize individualized preventive strategies for high-risk disease groups. We provide an overview and commentary on important advances in deriving and validating PRSs, as well as the implementation of PRSs for clinically useful purposes.