학술논문
Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
Document Type
Original Paper
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, Jr., 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. 55(12):2065-2074
Subject
Language
English
ISSN
1061-4036
1546-1718
1546-1718
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.
A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.
A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.