Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations
Authors: Thomas Minta , Su Yu-Ru , Rosenthal Elisabeth A. , Sakoda Lori C. , Schmit Stephanie L. , Timofeeva Maria N. , Chen Zhishan , Fernandez-Rozadilla Ceres , Law Philip J. , Murphy Neil , Carreras-Torres Robert , Diez-Obrero Virginia , van Duijnhoven Franzel J. B. , Jiang Shangqing , Shin Aesun , Wolk Alicja , Phipps Amanda I. , Burnett-Hartman Andrea , Gsur Andrea , Chan Andrew T. , Zauber Ann G. , Wu Anna H. , Lindblom Annika , Um Caroline Y. , Tangen Catherine M. , Gignoux Chris , Newton Christina , Haiman Christopher A. , Qu Conghui , Bishop D. Timothy , Buchanan Daniel D. , Crosslin David R. , Conti David V. , Kim Dong-Hyun , Hauser Elizabeth , White Emily , Siegel Erin , Schumacher Fredrick R. , Rennert Gad , Giles Graham G. , Hampel Heather , Brenner Hermann , Oze Isao , Oh Jae Hwan , Lee Jeffrey K. , Schneider Jennifer L. , Chang-Claude Jenny , Kim Jeongseon , Huyghe Jeroen R. , Zheng Jiayin , Hampe Jochen , Greenson Joel , Hopper John L. , Palmer Julie R. , Visvanathan Kala , Matsuo Keitaro , Matsuda Koichi , Jung Keum Ji , Li Li , Le Marchand Loic , Vodickova Ludmila , Bujanda Luis , Gunter Marc J. , Matejcic Marco , Jenkins Mark A. , Slattery Martha L. , D’Amato Mauro , Wang Meilin , Hoffmeister Michael , Woods Michael O. , Kim Michelle , Song Mingyang , Iwasaki Motoki , Du Mulong , Udaltsova Natalia , Sawada Norie , Vodicka Pavel , Campbell Peter T. , Newcomb Polly A. , Cai Qiuyin , Pearlman Rachel , Pai Rish K. , Schoen Robert E. , Steinfelder Robert S. , Haile Robert W. , Vandenputtelaar Rosita , Prentice Ross L. , Küry Sébastien , Castellví-Bel Sergi , Tsugane Shoichiro , 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. , Platz Elizabeth A. , Potter John D. , Li Christopher I. , Meester Reinier , Moreno Victor , Figueiredo Jane C. , Casey Graham , Lansdorp Vogelaar Iris , Dunlop Malcolm G. , Gruber Stephen B. , Hayes Richard B. , Pharoah Paul D. P. , Houlston Richard S. , Jarvik Gail P. , Tomlinson Ian P. , Zheng Wei , Corley Douglas A. , Peters Ulrike , Hsu Li 
Published: October 2023

AbstractPolygenic 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.