Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations.
Thomas M., Su Y-R., Rosenthal EA., Sakoda LC., Schmit SL., Timofeeva MN., Chen Z., Fernandez-Rozadilla C., Law PJ., Murphy N., Carreras-Torres R., Diez-Obrero V., van Duijnhoven FJB., Jiang S., Shin A., Wolk A., Phipps AI., Burnett-Hartman A., Gsur A., Chan AT., Zauber AG., Wu AH., Lindblom A., Um CY., Tangen CM., Gignoux C., Newton C., Haiman CA., Qu C., Bishop DT., Buchanan DD., Crosslin DR., Conti DV., Kim D-H., Hauser E., White E., Siegel E., Schumacher FR., Rennert G., Giles GG., Hampel H., Brenner H., Oze I., Oh JH., Lee JK., Schneider JL., Chang-Claude J., Kim J., Huyghe JR., Zheng J., Hampe J., Greenson J., Hopper JL., Palmer JR., Visvanathan K., Matsuo K., Matsuda K., Jung KJ., Li L., Le Marchand L., Vodickova L., Bujanda L., Gunter MJ., Matejcic M., Jenkins MA., Slattery ML., D'Amato M., Wang M., Hoffmeister M., Woods MO., Kim M., Song M., Iwasaki M., Du M., Udaltsova N., Sawada N., Vodicka P., Campbell PT., Newcomb PA., Cai Q., Pearlman R., Pai RK., Schoen RE., Steinfelder RS., Haile RW., Vandenputtelaar R., Prentice RL., Küry S., Castellví-Bel S., Tsugane S., Berndt SI., Lee SC., Brezina S., Weinstein SJ., Chanock SJ., Jee SH., Kweon S-S., Vadaparampil S., Harrison TA., Yamaji T., Keku TO., Vymetalkova V., Arndt V., Jia W-H., Shu X-O., Lin Y., Ahn Y-O., Stadler ZK., Van Guelpen B., Ulrich CM., Platz EA., Potter JD., Li CI., Meester R., Moreno V., Figueiredo JC., Casey G., Lansdorp Vogelaar I., Dunlop MG., Gruber SB., Hayes RB., Pharoah PDP., Houlston RS., Jarvik GP., Tomlinson IP., Zheng W., Corley DA., Peters U., Hsu L.
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