Affiliation:
1. Cardiovascular Research Center Massachusetts General Hospital Boston Massachusetts
Abstract
AbstractPolygenic risk scores (PRS) estimate genetic susceptibility of an individual to disease and have the potential of providing utility in multiple clinical contexts. However, their performance, computation, and reporting in diverse populations remain challenging. Here, we present a pragmatic approach to optimize a PRS for a population of interest that leverages publicly available data and methods and consists of seven steps that are easily implemented without the requirement of expertise in complex genetics: step 1, selecting source genome‐wide association studies (GWAS) and imputation; step 2, selecting methods to compute polygenic score; step 3, adjusting scores using principal components of genetic ancestry; step 4, selecting the best performing score; step 5, defining percentiles of a population distribution; step 6, validating performance of the optimized polygenic score; and step 7, implementing the optimized polygenic score in clinical practice. © 2023 Wiley Periodicals LLC.
Subject
Medical Laboratory Technology,Health Informatics,General Pharmacology, Toxicology and Pharmaceutics,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience