The concept of polygenic risk was initially coined in classic genetics, and it has been discussed and modeled since the early 20th century 1. With the advent of genome-wide association studies (GWAS), it has been possible to quantify polygenic risk with some precision in human complex traits, including psychiatric disorders 2. Polygenic risk scores (PRS) were first applied in psychiatry in 2009 by the International Schizophrenia Consortium 3, and the approach has since revolutionized psychiatric genomics research. However, it is not immediately clear—particularly to non-geneticists—how PRS are derived, what their limitations and applicability might be, and how PRS can best be used, now and in the future. This overview is focused toward guiding psychiatric practitioners and trainees, or informed non-geneticists, on the uses, today and in the coming decades, of PRS in psychiatry. Terms in italics are further defined in the accompanying “Glossary”.
