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

• Published in: Nature communications 2023-10, Vol.14 (1), p.6147-13, Article 6147
• Main Authors: Thomas, Minta, Su, Yu-Ru, Sakoda, Lori C., Schmit, Stephanie L., Timofeeva, Maria N., Chen, Zhishan, Fernandez-Rozadilla, Ceres, Law, Philip J., Murphy, Neil, Carreras-Torres, Robert, van Duijnhoven, Franzel J. B., Shin, Aesun, Wolk, Alicja, Phipps, Amanda I., Zauber, Ann G., Wu, Anna H., Um, Caroline Y., Tangen, Catherine M., Gignoux, Chris, Newton, Christina, Haiman, Christopher A., Qu, Conghui, Bishop, D. Timothy, Buchanan, Daniel D., Crosslin, David R., Kim, Dong-Hyun, Hauser, Elizabeth, White, Emily, Siegel, Erin, Rennert, Gad, Giles, Graham G., Hampel, Heather, Brenner, Hermann, Oze, Isao, Lee, Jeffrey K., Kim, Jeongseon, Huyghe, Jeroen R., Zheng, Jiayin, Hampe, Jochen, Greenson, Joel, Palmer, Julie R., Visvanathan, Kala, Matsuo, Keitaro, Jung, Keum Ji, Li, Li, Le Marchand, Loic, Vodickova, Ludmila, Bujanda, Luis, Matejcic, Marco, Jenkins, Mark A., Slattery, Martha L., D’Amato, Mauro, Hoffmeister, Michael, Woods, Michael O., Kim, Michelle, Song, Mingyang, Iwasaki, Motoki, Du, Mulong, Sawada, Norie, Vodicka, Pavel, Campbell, Peter T., Pearlman, Rachel, Pai, Rish K., Prentice, Ross L., Küry, Sébastien, Castellví-Bel, Sergi, Berndt, Sonja I., Lee, Soo Chin, Brezina, Stefanie, Weinstein, Stephanie J., Chanock, Stephen J., Jee, Sun Ha, Kweon, Sun-Seog, Vadaparampil, Susan, Harrison, Tabitha A., Yamaji, Taiki, Keku, Temitope O., Vymetalkova, Veronika, Arndt, Volker, Jia, Wei-Hua, Shu, Xiao-Ou, Lin, Yi, Ahn, Yoon-Ok, Stadler, Zsofia K., Van Guelpen, Bethany, Ulrich, Cornelia M., Li, Christopher I., Meester, Reinier, Moreno, Victor, Figueiredo, Jane C., Casey, Graham, Lansdorp Vogelaar, Iris, Dunlop, Malcolm G., Hayes, Richard B., Pharoah, Paul D. P., Houlston, Richard S., Jarvik, Gail P., Tomlinson, Ian P., Zheng, Wei, Corley, Douglas A.
• Format: Article
• Language: English
• Subjects: 631/208/205/2138; 631/67/2322; 692/53/2423; 692/699/67/68; Cancer; Colorectal cancer; Colorectal carcinoma; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Datasets; Ethnic factors; Ethnicity - genetics; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study; Genomes; Hispanic people; Humanities and Social Sciences; Humans; Medicin och hälsovetenskap; Minority & ethnic groups; multidisciplinary; Multifactorial Inheritance; Polymorphism, Single Nucleotide; Populations; Risk; Risk Factors; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-41819-0

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