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research article

Improving polygenic prediction with genetically inferred ancestry

Naret, Olivier  
•
Kutalik, Zoltan
•
Hodel, Flavia  
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July 14, 2022
Human Genetics And Genomics Advances

Genome-wide association studies (GWASs) have demonstrated that most common diseases have a strong genetic component from many genetic variants each with a small effect size. GWAS summary statistics have allowed the construction of polygenic scores (PGSs) estimating part of the individual risk for common diseases. Here, we propose to improve PGS-based risk estimation by incorporating genetic ancestry derived from genome-wide genotyping data. Our method involves three cohorts: a base (or discovery) for association studies, a target for phenotype/risk prediction, and a map for ancestry mapping; successively, (1) it generates for each individual in the base and target cohorts a set of principal components based on the map cohort-called mapped PCs, (2) it associates in the base cohort the phenotype with the mapped-PCs, and (3) it uses the mapped PCs in the target cohort to generate a phenotypic predictor called the ancestry score. We evaluated the ancestry score by comparing a predictive model using a PGS with one combining a PGS and an ancestry score. First, we performed simulations and found that the ancestry score has a greater impact on traits that correlate with ancestry-specific variants. Second, we showed, using UK Biobank data, that the ancestry score improves genetic prediction for our nine phenotypes to very different degrees. Third, we performed simulations and found that the more heterogeneous the base and target cohorts, the more beneficial the ancestry score is. Finally, we validated our approach under realistic conditions with UK Biobank as the base cohort and Swiss individuals from the CoLaus vertical bar PsyCoLaus study as the target cohort.

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Type
research article
DOI
10.1016/j.xhgg.2022.100109
Web of Science ID

WOS:000792969700002

Author(s)
Naret, Olivier  
Kutalik, Zoltan
Hodel, Flavia  
Xu, Zhi Ming  
Marques-Vidal, Pedro
Fellay, Jacques  
Date Issued

2022-07-14

Publisher

ELSEVIER

Published in
Human Genetics And Genomics Advances
Volume

3

Issue

3

Article Number

100109

Subjects

Genetics & Heredity

•

risk scores

•

association

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health

•

disease

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
UPFELLAY  
Available on Infoscience
May 23, 2022
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/188078
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