Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

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

Authors/Creators:	Thomas, M. https://orcid.org/0000-0001-9337-7015 Su, Y.-R. Rosenthal, E.A. https://orcid.org/0000-0001-6042-4487 Sakoda, L.C. https://orcid.org/0000-0002-0900-5735 Schmit, S.L. https://orcid.org/0000-0001-5931-1194 Timofeeva, M.N. https://orcid.org/0000-0002-2503-4253 Chen, Z. Fernandez-Rozadilla, C. https://orcid.org/0000-0001-7330-4804 Law, P.J. https://orcid.org/0000-0001-9663-4611 Murphy, N. https://orcid.org/0000-0003-3347-8249 Carreras-Torres, R. https://orcid.org/0000-0002-2925-734X Diez-Obrero, V. van Duijnhoven, F.J.B. Jiang, S. Shin, A. https://orcid.org/0000-0002-6426-1969 Wolk, A. https://orcid.org/0000-0001-7387-6845 Phipps, A.I. Burnett-Hartman, A. Gsur, A. https://orcid.org/0000-0002-9795-1528 Chan, A.T. https://orcid.org/0000-0001-7284-6767 Zauber, A.G. https://orcid.org/0000-0002-1764-5994 Wu, A.H. Lindblom, A. Um, C.Y. https://orcid.org/0000-0001-5449-6230 Tangen, C.M. Gignoux, C. https://orcid.org/0000-0001-9728-6567 Newton, C. Haiman, C.A. Qu, C. Bishop, D.T. https://orcid.org/0000-0002-8752-8785 Buchanan, D.D. https://orcid.org/0000-0003-2225-6675 Crosslin, D.R. Conti, D.V. Kim, D.-H. Hauser, E. White, E. Siegel, E. https://orcid.org/0000-0003-1779-2510 Schumacher, F.R. https://orcid.org/0000-0002-3073-7463 Rennert, G. https://orcid.org/0000-0002-8512-068X Giles, G.G. https://orcid.org/0000-0003-4946-9099 Hampel, H. https://orcid.org/0000-0001-7558-9794 Brenner, H. https://orcid.org/0000-0002-6129-1572 Oze, I. https://orcid.org/0000-0002-0762-1147 Oh, J.H. Lee, J.K. Schneider, J.L. Chang-Claude, J. https://orcid.org/0000-0001-8919-1971 Kim, J. https://orcid.org/0000-0002-0889-2686 Huyghe, J.R. https://orcid.org/0000-0001-6027-9806 Zheng, J. https://orcid.org/0000-0002-5559-6847 Hampe, J. https://orcid.org/0000-0002-2421-6127 Greenson, J. Hopper, J.L. Palmer, J.R. Visvanathan, K. https://orcid.org/0000-0002-0582-8005 Matsuo, K. https://orcid.org/0000-0003-1761-6314 Matsuda, K. https://orcid.org/0000-0001-7292-2686 Jung, K.J. https://orcid.org/0000-0003-4993-0666 Li, L. Le Marchand, L. Vodickova, L. Bujanda, L. https://orcid.org/0000-0002-4353-9968 Gunter, M.J. Matejcic, M. Jenkins, M.A. https://orcid.org/0000-0002-8964-6160 Slattery, M.L. D’Amato, M. Wang, M. https://orcid.org/0000-0002-4996-958X Hoffmeister, M. https://orcid.org/0000-0002-8307-3197 Woods, M.O. Kim, M. Song, M. https://orcid.org/0000-0002-1324-0316 Iwasaki, M. Du, M. https://orcid.org/0000-0002-2733-6490 Udaltsova, N. Sawada, N. https://orcid.org/0000-0002-9936-1476 Vodicka, P. Campbell, P.T. Newcomb, P.A. https://orcid.org/0000-0001-8786-0043 Cai, Q. https://orcid.org/0000-0002-9384-5648 Pearlman, R. Pai, R.K. Schoen, R.E. https://orcid.org/0000-0001-7153-2766 Steinfelder, R.S. Haile, R.W. https://orcid.org/0000-0001-6902-1836 Vandenputtelaar, R. Prentice, R.L. Küry, S. https://orcid.org/0000-0001-5497-0465 Castellví-Bel, S. https://orcid.org/0000-0003-1217-5097 Tsugane, S. https://orcid.org/0000-0003-4105-2774 Berndt, S.I. Lee, S.C. Brezina, S. https://orcid.org/0000-0001-5238-6900 Weinstein, S.J. https://orcid.org/0000-0002-3834-1535 Chanock, S.J. https://orcid.org/0000-0002-2324-3393 Jee, S.H. Kweon, S.-S. Vadaparampil, S. Harrison, T.A. https://orcid.org/0000-0002-4173-7530 Yamaji, T. Keku, T.O. Vymetalkova, V. Arndt, V. https://orcid.org/0000-0001-9320-8684 Jia, W.-H. https://orcid.org/0000-0002-0528-8715 Shu, X.-O. Lin, Y. Ahn, Y.-O. Stadler, Z.K. https://orcid.org/0000-0002-6985-2864 Van Guelpen, B. https://orcid.org/0000-0002-9692-101X Ulrich, C.M. https://orcid.org/0000-0001-7641-059X Platz, E.A. https://orcid.org/0000-0003-3676-8954 Potter, J.D. https://orcid.org/0000-0001-5439-1500 Li, C.I. Meester, R. Moreno, V. https://orcid.org/0000-0002-2818-5487 Figueiredo, J.C. Casey, G. Lansdorp Vogelaar, I. Dunlop, M.G. https://orcid.org/0000-0002-3033-5851 Gruber, S.B. https://orcid.org/0000-0001-8656-7822 Hayes, R.B. https://orcid.org/0000-0002-0918-661X Pharoah, P.D.P. https://orcid.org/0000-0001-8494-732X Houlston, R.S. https://orcid.org/0000-0002-5268-0242 Jarvik, G.P. Tomlinson, I.P. https://orcid.org/0000-0003-3037-1470 Zheng, W. https://orcid.org/0000-0003-1226-070X Corley, D.A. Peters, U. https://orcid.org/0000-0001-5666-9318 Hsu, L. https://orcid.org/0000-0001-8168-4712
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:	Accepted: 19 September 2023 Published (online): 2 October 2023 Published: 2 October 2023
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:	https://doi.org/10.1038/s41467-023-41819-0
Related URLs:	PubMed URL Dataset Dataset Dataset Dataset

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Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

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Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

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