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Cited by 271Genetic Associations and EpidemiologyGenetic and phenotypic traits in livestockRace, Genetics, and Society

Theoretical and empirical quantification of the accuracy of polygenic scores in ancestry divergent populations

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Wang, Ying, Guo, Jing, Ni, Guiyan, Yang, Jian, Visscher, Peter M., Yengo, Loic·2020·Nature Communications
DOI 10.1038/s41467-020-17719-yPMC PMC7395791

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Abstract

Polygenic scores (PGS) have been widely used to predict disease risk using variants identified from genome-wide association studies (GWAS). To date, most GWAS have been conducted in populations of European ancestry, which limits the use of GWAS-derived PGS in non-European ancestry populations. Here, we derive a theoretical model of the relative accuracy (RA) of PGS across ancestries. We show through extensive simulations that the RA of PGS based on genome-wide significant SNPs can be predicted accurately from modelling linkage disequilibrium (LD), minor allele frequencies (MAF), cross-population correlations of causal SNP effects and heritability. We find that LD and MAF differences between ancestries can explain between 70 and 80% of the loss of RA of European-based PGS in African ancestry for traits like body mass index and type 2 diabetes. Our results suggest that causal variants underlying common genetic variation identified in European ancestry GWAS are mostly shared across continents.

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Cited by

Sorted by citations

Authors
Wang, Y., Guo, J., Ni, G., Yang, J., Visscher, P. M., & Yengo, L.
Affiliations
The University of Queensland (AU)
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-07-31
Volume
11
Issue
1
Pages
3865-3865
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-020-17719-y
PMC
PMC7395791
OpenAlex
W3046366876
Cited by
271
References
13
Citations by year
2026: 48 · 2025: 35 · 2024: 56 · 2023: 45 · 2022: 56 · 2021: 24 · 2020: 6 · 2018: 1
FWCI
19.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Department of Health | National Health and Medical Research Council (1113400)
  • Australian Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Race, Genetics, and Society
Keywords
polygenic risk score, cross-population prediction, relative accuracy, linkage disequilibrium, minor allele frequency, heritability, African ancestry, body mass index, type 2 diabetes, common genetic variants
MeSH terms
Adult, Africa, Aged, Alleles, Asia, Asthma, Cholesterol, Computer Simulation, Diabetes Mellitus, Type 2, Europe, Female, Gene Frequency, Humans, Hypertension, Male, Middle Aged, Models, Genetic, Prognosis, Risk, Linkage Disequilibrium, Body Mass Index, Quantitative Trait, Heritable, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Genome-Wide Association Study

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