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shaPRS: Leveraging shared genetic effects across traits or ancestries improves accuracy of polygenic scores.

Published version
Peer-reviewed

Repository DOI


Type

Article

Change log

Authors

Vigorito, Elena 
Fachal, Laura 
Anderson, Carl A 

Abstract

We present shaPRS, a method that leverages widespread pleiotropy between traits or shared genetic effects across ancestries, to improve the accuracy of polygenic scores. The method uses genome-wide summary statistics from two diseases or ancestries to improve the genetic effect estimate and standard error at SNPs where there is homogeneity of effect between the two datasets. When there is significant evidence of heterogeneity, the genetic effect from the disease or population closest to the target population is maintained. We show via simulation and a series of real-world examples that shaPRS substantially enhances the accuracy of polygenic risk scores (PRSs) for complex diseases and greatly improves PRS performance across ancestries. shaPRS is a PRS pre-processing method that is agnostic to the actual PRS generation method, and as a result, it can be integrated into existing PRS generation pipelines and continue to be applied as more performant PRS methods are developed over time.

Description

Keywords

PGS, PRS, cross-ancestry, genetic correlation, pleiotropy, polygenic score, shaPRS, trans-ethnic, Multifactorial Inheritance, Humans, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Models, Genetic, Computer Simulation, Genetic Pleiotropy, Phenotype

Journal Title

Am J Hum Genet

Conference Name

Journal ISSN

0002-9297
1537-6605

Volume Title

111

Publisher

Elsevier BV
Sponsorship
Wellcome Trust (107881/Z/15/Z)
Wellcome Trust (203950/Z/16/Z)
Medical Research Council (MC_UU_00002/4)
Wellcome Trust (220788/Z/20/Z)
National Institute for Health and Care Research (IS-BRC-1215-20014)