Principles and methods for transferring polygenic risk scores across global populations

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Linda Kachuri, Nilanjan Chatterjee, Jibril Hirbo, Daniel J Schaid, Bogdan Pasaniuc, Rohan Bhukar, John S Witte, Tian Ge

Published: 24 Aug 2023, Last Modified: 12 Sept 2025Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.EveryoneRevisionsCC BY-NC-ND 4.0
Abstract: Polygenic risk scores (PRSs) summarize the genetic predisposition of a complex human trait or disease and may become a valuable tool for advancing precision medicine. However, PRSs that are developed in populations of predominantly European genetic ancestries can increase health disparities due to poor predictive performance in individuals of diverse and complex genetic ancestries. We describe genetic and modifiable risk factors that limit the transferability of PRSs across populations and review the strengths and weaknesses of existing PRS construction methods for diverse ancestries. Developing PRSs that benefit global populations in research and clinical settings provides an opportunity for innovation and is essential for health equity.