Polygenic transcriptome risk scores (PTRS) can improve portability of polygenic risk scores across ancestries

BACKGROUND: Polygenic risk scores (PRS) are valuable to translate the results of genome-wide association studies (GWAS) into clinical practice. To date, most GWAS have been based on individuals of European-ancestry leading to poor performance in populations of non-European ancestry. RESULTS: We intr...

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Autores principales: Liang, Yanyu, Pividori, Milton, Manichaikul, Ani, Palmer, Abraham A., Cox, Nancy J., Wheeler, Heather E., Im, Hae Kyung
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Research
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759285/
https://www.ncbi.nlm.nih.gov/pubmed/35027082
http://dx.doi.org/10.1186/s13059-021-02591-w
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author Liang, Yanyu
Pividori, Milton
Manichaikul, Ani
Palmer, Abraham A.
Cox, Nancy J.
Wheeler, Heather E.
Im, Hae Kyung
author_facet Liang, Yanyu
Pividori, Milton
Manichaikul, Ani
Palmer, Abraham A.
Cox, Nancy J.
Wheeler, Heather E.
Im, Hae Kyung
author_sort Liang, Yanyu
collection PubMed
description BACKGROUND: Polygenic risk scores (PRS) are valuable to translate the results of genome-wide association studies (GWAS) into clinical practice. To date, most GWAS have been based on individuals of European-ancestry leading to poor performance in populations of non-European ancestry. RESULTS: We introduce the polygenic transcriptome risk score (PTRS), which is based on predicted transcript levels (rather than SNPs), and explore the portability of PTRS across populations using UK Biobank data. CONCLUSIONS: We show that PTRS has a significantly higher portability (Wilcoxon p=0.013) in the African-descent samples where the loss of performance is most acute with better performance than PRS when used in combination. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s13059-021-02591-w).
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spelling pubmed-87592852022-01-18 Polygenic transcriptome risk scores (PTRS) can improve portability of polygenic risk scores across ancestries Liang, Yanyu Pividori, Milton Manichaikul, Ani Palmer, Abraham A. Cox, Nancy J. Wheeler, Heather E. Im, Hae Kyung Genome Biol Research BACKGROUND: Polygenic risk scores (PRS) are valuable to translate the results of genome-wide association studies (GWAS) into clinical practice. To date, most GWAS have been based on individuals of European-ancestry leading to poor performance in populations of non-European ancestry. RESULTS: We introduce the polygenic transcriptome risk score (PTRS), which is based on predicted transcript levels (rather than SNPs), and explore the portability of PTRS across populations using UK Biobank data. CONCLUSIONS: We show that PTRS has a significantly higher portability (Wilcoxon p=0.013) in the African-descent samples where the loss of performance is most acute with better performance than PRS when used in combination. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at (10.1186/s13059-021-02591-w). BioMed Central 2022-01-13 /pmc/articles/PMC8759285/ /pubmed/35027082 http://dx.doi.org/10.1186/s13059-021-02591-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Liang, Yanyu
Pividori, Milton
Manichaikul, Ani
Palmer, Abraham A.
Cox, Nancy J.
Wheeler, Heather E.
Im, Hae Kyung
Polygenic transcriptome risk scores (PTRS) can improve portability of polygenic risk scores across ancestries
title Polygenic transcriptome risk scores (PTRS) can improve portability of polygenic risk scores across ancestries
title_full Polygenic transcriptome risk scores (PTRS) can improve portability of polygenic risk scores across ancestries
title_fullStr Polygenic transcriptome risk scores (PTRS) can improve portability of polygenic risk scores across ancestries
title_full_unstemmed Polygenic transcriptome risk scores (PTRS) can improve portability of polygenic risk scores across ancestries
title_short Polygenic transcriptome risk scores (PTRS) can improve portability of polygenic risk scores across ancestries
title_sort polygenic transcriptome risk scores (ptrs) can improve portability of polygenic risk scores across ancestries
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8759285/
https://www.ncbi.nlm.nih.gov/pubmed/35027082
http://dx.doi.org/10.1186/s13059-021-02591-w
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