POLYGENIC RISK SCORES FOR COMPLEX DISEASE PREDICTION: CLINICAL UTILITY AND IMPLEMENTATION CHALLENGES

Abstract

Genome-wide association studies conducted over the past two decades have consistently shown that common complex diseases, including cardiovascular disease, diabetes, and most cancers, are influenced not by a small number of high-effect genetic variants but by hundreds to thousands of individually weak-effect single nucleotide polymorphisms distributed across the genome. Polygenic risk scores aggregate these numerous small-effect associations into a single quantitative metric intended to capture an individual's inherited liability to a given complex disease, an approach that has moved rapidly from a primarily research-oriented tool toward active consideration for routine clinical risk stratification [1].