학술논문
Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
Document Type
Article
Author
Wang, Anqi; Shen, Jiayi; Rodriguez, Alex A.; Saunders, Edward J.; Chen, Fei; Janivara, Rohini; Darst, Burcu F.; Sheng, Xin; Xu, Yili; Chou, Alisha J.; Benlloch, Sara; Dadaev, Tokhir; Brook, Mark N.; Plym, Anna; Sahimi, Ali; Hoffman, Thomas J.; Takahashi, Atushi; Matsuda, Koichi; Momozawa, Yukihide; Fujita, Masashi; Laisk, Triin; Figuerêdo, Jéssica; Muir, Kenneth; Ito, Shuji; Liu, Xiaoxi; Uchio, Yuji; Kubo, Michiaki; Kamatani, Yoichiro; Lophatananon, Artitaya; Wan, Peggy; Andrews, Caroline; Lori, Adriana; Choudhury, Parichoy P.; Schleutker, Johanna; Tammela, Teuvo L. J.; Sipeky, Csilla; Auvinen, Anssi; Giles, Graham G.; Southey, Melissa C.; MacInnis, Robert J.; Cybulski, Cezary; Wokolorczyk, Dominika; Lubinski, Jan; Rentsch, Christopher T.; Cho, Kelly; Mcmahon, Benjamin H.; Neal, David E.; Donovan, Jenny L.; Hamdy, Freddie C.; Martin, Richard M.; Nordestgaard, Borge G.; Nielsen, Sune F.; Weischer, Maren; Bojesen, Stig E.; Røder, Andreas; Stroomberg, Hein V.; Batra, Jyotsna; Chambers, Suzanne; Horvath, Lisa; Clements, Judith A.; Tilly, Wayne; Risbridger, Gail P.; Gronberg, Henrik; Aly, Markus; Szulkin, Robert; Eklund, Martin; Nordstrom, Tobias; Pashayan, Nora; Dunning, Alison M.; Ghoussaini, Maya; Travis, Ruth C.; Key, Tim J.; Riboli, Elio; Park, Jong Y.; Sellers, Thomas A.; Lin, Hui-Yi; Albanes, Demetrius; Weinstein, Stephanie; Cook, Michael B.; Mucci, Lorelei A.; Giovannucci, Edward; Lindstrom, Sara; Kraft, Peter; Hunter, David J.; Penney, Kathryn L.; Turman, Constance; Tangen, Catherine M.; Goodman, Phyllis J.; Thompson, Ian M.; Hamilton, Robert J.; Fleshner, Neil E.; Finelli, Antonio; Parent, Marie-Élise; Stanford, Janet L.; Ostrander, Elaine A.; Koutros, Stella; Beane Freeman, Laura E.; Stampfer, Meir; Wolk, Alicja; Håkansson, Niclas; Andriole, Gerald L.; Hoover, Robert N.; Machiela, Mitchell J.; Sørensen, Karina Dalsgaard; Borre, Michael; Blot, William J.; Zheng, Wei; Yeboah, Edward D.; Mensah, James E.; Lu, Yong-Jie; Zhang, Hong-Wei; Feng, Ninghan; Mao, Xueying; Wu, Yudong; Zhao, Shan-Chao; Sun, Zan; Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.; West, Catharine M. L.; Barnett, Gill; Maier, Christiane; Schnoeller, Thomas; Luedeke, Manuel; Kibel, Adam S.; Drake, Bettina F.; Cussenot, Olivier; Cancel-Tassin, Geraldine; Menegaux, Florence; Truong, Thérèse; Koudou, Yves Akoli; John, Esther M.; Grindedal, Eli Marie; Maehle, Lovise; Khaw, Kay-Tee; Ingles, Sue A.; Stern, Mariana C.; Vega, Ana; Gómez-Caamaño, Antonio; Fachal, Laura; Rosenstein, Barry S.; Kerns, Sarah L.; Ostrer, Harry; Teixeira, Manuel R.; Paulo, Paula; Brandão, Andreia; Watya, Stephen; Lubwama, Alexander; Bensen, Jeannette T.; Butler, Ebonee N.; Mohler, James L.; Taylor, Jack A.; Kogevinas, Manolis; Dierssen-Sotos, Trinidad; Castaño-Vinyals, Gemma; Cannon-Albright, Lisa; Teerlink, Craig C.; Huff, Chad D.; Pilie, Patrick; Yu, Yao; Bohlender, Ryan J.; Gu, Jian; Strom, Sara S.; Multigner, Luc; Blanchet, Pascal; Brureau, Laurent; Kaneva, Radka; Slavov, Chavdar; Mitev, Vanio; Leach, Robin J.; Brenner, Hermann; Chen, Xuechen; Holleczek, Bernd; Schöttker, Ben; Klein, Eric A.; Hsing, Ann W.; Kittles, Rick A.; Murphy, Adam B.; Logothetis, Christopher J.; Kim, Jeri; Neuhausen, Susan L.; Steele, Linda; Ding, Yuan Chun; Isaacs, William B.; Nemesure, Barbara; Hennis, Anselm J. M.; Carpten, John; Pandha, Hardev; Michael, Agnieszka; De Ruyck, Kim; De Meerleer, Gert; Ost, Piet; Xu, Jianfeng; Razack, Azad; Lim, Jasmine; Teo, Soo-Hwang; Newcomb, Lisa F.; Lin, Daniel W.; Fowke, Jay H.; Neslund-Dudas, Christine M.; Rybicki, Benjamin A.; Gamulin, Marija; Lessel, Davor; Kulis, Tomislav; Usmani, Nawaid; Abraham, Aswin; Singhal, Sandeep; Parliament, Matthew; Claessens, Frank; Joniau, Steven; Van den Broeck, Thomas; Gago-Dominguez, Manuela; Castelao, Jose Esteban; Martinez, Maria Elena; Larkin, Samantha; Townsend, Paul A.; Aukim-Hastie, Claire; Bush, William S.; Aldrich, Melinda C.; Crawford, Dana C.; Srivastava, Shiv; Cullen, Jennifer; Petrovics, Gyorgy; Casey, Graham; Wang, Ying; Tettey, Yao; Lachance, Joseph; Tang, Wei; Biritwum, Richard B.; Adjei, Andrew A.; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Yamoah, Kosj; Govindasami, Koveela; Chokkalingam, Anand P.; Keaton, Jacob M.; Hellwege, Jacklyn N.; Clark, Peter E.; Jalloh, Mohamed; Gueye, Serigne M.; Niang, Lamine; Ogunbiyi, Olufemi; Shittu, Olayiwola; Amodu, Olukemi; Adebiyi, Akindele O.; Aisuodionoe-Shadrach, Oseremen I.; Ajibola, Hafees O.; Jamda, Mustapha A.; Oluwole, Olabode P.; Nwegbu, Maxwell; Adusei, Ben; Mante, Sunny; Darkwa-Abrahams, Afua; Diop, Halimatou; Gundell, Susan M.; Roobol, Monique J.; Jenster, Guido; van Schaik, Ron H. N.; Hu, Jennifer J.; Sanderson, Maureen; Kachuri, Linda; Varma, Rohit; McKean-Cowdin, Roberta; Torres, Mina; Preuss, Michael H.; Loos, Ruth J. F.; Zawistowski, Matthew; Zöllner, Sebastian; Lu, Zeyun; Van Den Eeden, Stephen K.; Easton, Douglas F.; Ambs, Stefan; Edwards, Todd L.; Mägi, Reedik; Rebbeck, Timothy R.; Fritsche, Lars; Chanock, Stephen J.; Berndt, Sonja I.; Wiklund, Fredrik; Nakagawa, Hidewaki; Witte, John S.; Gaziano, J. Michael; Justice, Amy C.; Mancuso, Nick; Terao, Chikashi; Eeles, Rosalind A.; Kote-Jarai, Zsofia; Madduri, Ravi K.; Conti, David V.; Haiman, Christopher A.
Source
Nature Genetics; December 2023, Vol. 55 Issue: 12 p2065-2074, 10p
Subject
Language
ISSN
10614036; 15461718
Abstract
The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P= 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.