Thomas, M. orcid.org/0000-0001-9337-7015, Su, Y.-R., Rosenthal, E.A. orcid.org/0000-0001-6042-4487 et al. (126 more authors) (2023) Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations. Nature Communications, 14. 6147. ISSN 2041-1723
Abstract
Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2023. 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/. |
Keywords: | Humans; Colorectal Neoplasms; Genetic Predisposition to Disease; Risk Factors; Multifactorial Inheritance; Polymorphism, Single Nucleotide; Genome-Wide Association Study; Ethnicity |
Dates: |
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Institution: | The University of Leeds |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Dec 2023 12:40 |
Last Modified: | 15 Dec 2023 12:40 |
Published Version: | https://www.nature.com/articles/s41467-023-41819-0 |
Status: | Published |
Publisher: | Springer |
Identification Number: | 10.1038/s41467-023-41819-0 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:206626 |