What Are Polygenic Scores and Why Are They Important?

Mendelian disorders and monogenic traits result from combinations of variants in 1 or a few genes that have a large effect on the propensity for developing a certain disease or characteristic. In contrast, complex traits, such as eye color or cardiovascular disease, are determined by variations occurring in many genes that have smaller effect sizes and act over long periods of time, often in concert with environmental factors. The cumulative risk derived from aggregating contributions of the many DNA variants associated with a complex trait or disease is referred to as a polygenic risk score (also known as a genetic risk score). This JAMA Genomics and Precision Health article explains polygenic risk scores as determinants of an individual’s inherited risk for complex disease.