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Principles and methods for transferring polygenic risk scores across global populations

by Pasaniuc, Bogdan , Kachuri, Linda , Kenny, Eimear E , Conti, David V , Wang, Ying , Auer, Paul L , Hirbo, Jibril , Kullo, Iftikhar J , Zhang, Yuji , Martin, Iman , Ding, Yi , Zhang, Haoyu , Chatterjee, Nilanjan , Conomos, Matthew P , Ge, Tian , Schaid, Daniel J , Witte, John S

in Accuracy / Disease / Genealogy / Genetic diversity / Genetic factors / Genetics / Genomes / Polygenic inheritance / Population / Population genetics / Precision medicine / Risk factors

2024

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Principles and methods for transferring polygenic risk scores across global populations

in Accuracy / Disease / Genealogy / Genetic diversity / Genetic factors / Genetics / Genomes / Polygenic inheritance / Population / Population genetics / Precision medicine / Risk factors

2024

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Principles and methods for transferring polygenic risk scores across global populations

in Accuracy / Disease / Genealogy / Genetic diversity / Genetic factors / Genetics / Genomes / Polygenic inheritance / Population / Population genetics / Precision medicine / Risk factors

2024

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Journal Article

Principles and methods for transferring polygenic risk scores across global populations

Pasaniuc, Bogdan,

Kachuri, Linda,

Kenny, Eimear E,

Conti, David V,

Wang, Ying,

Auer, Paul L,

Hirbo, Jibril,

Kullo, Iftikhar J,

Zhang, Yuji,

Martin, Iman,

Ding, Yi,

Zhang, Haoyu,

Chatterjee, Nilanjan,

Conomos, Matthew P,

Ge, Tian,

Schaid, Daniel J,

Witte, John S

2024

Overview

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.This Review summarizes the genetic and non-genetic factors that impact the transferability of polygenic risk scores (PRSs) across populations, highlighting the technical challenges of existing PRS construction methods for diverse ancestries and the emerging resources for more widespread use of PRSs.

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Publisher

Nature Publishing Group

Subject

/ Disease

/ Genomes