Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants

作者：Anqi Wang, Jiayi Shen, Alex A Rodriguez, Edward J. Saunders, Fei Chen, Rohini Janivara, Burcu F. Darst, Xin Sheng, Yili Xu, Alisha Chou, Sara Benlloch, Tokhir Dadaev, Mark N. Brook, Anna Plym, Ali Sahimi, Thomas J. Hoffman, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi Fujita, Triin Laisk, Jéssica Figuerêdo, Kenneth Muir, Shuji Ito, Xiaoxi Liu, The Biobank Japan Project, Yuji Yamanashi, Yoichi Furukawa, Takayuki Morisaki, Yoshinori Murakami, Kaori Muto, Akiko Nagai, Wataru Obara, Ken Yamaji, Kazuhisa Takahashi, Satoshi Asai, Yasuo Takahashi, Takao Suzuki, Nobuaki Sinozaki, Hiroki Yamaguchi, Shiro Minami, Shigeo Murayama, Kozo Yoshimori, Satoshi Nagayama, Daisuke Obata, Masahiko Higashiyama, Akihide Masumoto, Yukihiro Koretsune, Yuji Uchio, Michiaki Kubo, Yoichiro Kamatani, Artitaya Lophatananon, Peggy Wan, Caroline Andrews, Adriana Lori, Parichoy Pal Choudhury, Johanna Schleutker, Teuvo L. J. Tammela, Csilla Sipeky, Anssi Auvinen, Graham G. Giles, Melissa C. Southey, Robert J. MacInnis, Cezary Cybulski, Dominika Wokołorczyk, Jan Lubiński, Christopher T. Rentsch, Kelly Cho, Benjamin H. McMahon, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Børge G. Nordestgaard, Sune F. Nielsen, Maren Weischer, Stig E. Bojesen, Martin Andreas Røder, Hein Vincent Stroomberg, Jyotsna Batra, Suzanne K. Chambers, Lisa G. Horvath, Judith A. Clements, Wayne D. Tilley, Gail P. Risbridger, Henrik Grönberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordström, Nora Pashayan, Alison M. Dunning, Maya Ghoussaini, Ruth C. Travis, Timothy J. Key, Elio Ríboli, Jong Y. Park, Thomas A. Sellers, Hui‐Yi Lin, Demetrius Albanes, Stephanie J. Weinstein, Michael B. Cook, Lorelei A. Mucci, Edward L. Giovannucci, Sara Lindström, Peter Kraft, David J. Hunter, Kathryn L. Penney, Constance Turman, Catherine M. Tangen, Phyllis J. Goodman, Ian M. Thompson, Robert J. Hamilton, Neil E. Fleshner, Antonio Finelli, Marie‐Élise Parent, Janet L. Stanford, Elaine A. Ostrander, Stella Koutros, Laura E. Beane Freeman, Meir J. Stampfer, Alicja Wolk, Niclas Håkansson, Gerald L. Andriole, Robert N. Hoover, Mitchell J. Machiela, Karina D. Sørensen, Michael Borre, William J. Blot, Wei Zheng, Edward D. Yeboah, James E. Mensah, Yong‐Jie Lu, Hongwei Zhang, Ninghan Feng, Xueying Mao, Yudong Wu, Shan‐Chao Zhao, Zan Sun, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Catharine West, Gill Barnett, Christiane Maier, Thomas Schnoeller, Manuel Luedeke, Adam S. Kibel, Bettina F. Drake, Olivier Cussenot, Géraldine Cancel‐Tassin, F. Ménégaux, Thérèse Truong, Yves Akoli Koudou, Esther M. John, Eli Marie Grindedal, Lovise Mæhle, Kay-Tee Khaw, Sue A. Ingles, Mariana C. Stern, Ana Vega, Antonio Gómez‐Caamaño, Laura Fachal, Barry S. Rosenstein, Sarah L. Kerns, Harry Ostrer, Manuel R. Teixeira, Paula Paulo, Andreia Brandão, Stephen Watya, Alexander Lubwama, Jeannette T. Bensen, Eboneé N. Butler, James L. Mohler, Jack A. Taylor, Manolis Kogevinas, Trinidad Dierssen-Sotos, Gemma Castaño‐Vinyals, Lisa Cannon‐Albright, Craig C. Teerlink, Chad Huff, Patrick G. Pilié, Yao Yu, Ryan J. Bohlender, Jian Gu, Sara S. Strom, Luc Multigner, Pascal Blanchet, Laurent Brureau, Radka Kaneva, Chavdar Slavov, Vanio Mitev, Robin J. Leach, Hermann Brenner, Xuechen Chen, Bernd Holleczek, Ben Schöttker, Eric A. Klein, Ann W. Hsing, Rick A. Kittles, Adam B. Murphy, Christopher J. Logothetis, Jeri Kim, Susan L. Neuhausen, Linda Steele, Yuan Chun Ding, William B. Isaacs, Barbara Nemesure, Anselm J. M. Hennis, John D. Carpten, Hardev Pandha, Agnieszka Michael, Kim De Ruyck, Gert De Meerleer, Piet Ost, Jianfeng Xu, Azad Hassan Abdul Razack, Jasmine Lim, Soo‐Hwang Teo, Lisa F. Newcomb, Daniel Lin, Jay H. Fowke, Christine M. Neslund-Dudas, Benjamin A. Rybicki, Marija Gamulin, Davor Lessel, Tomislav Kuliš, Nawaid Usmani, Aswin Abraham, Sandeep K. Singhal, Matthew Parliament, Frank Claessens, Steven Joniau, Thomas Van den Broeck, Manuela Gago-Domínguez, Jose E. Castelao, Maria Elena Martinez, Samantha Larkin, Paul A. Townsend, Claire Aukim-Hastie, William S. Bush, Melinda C. Aldrich, Dana C. Crawford, Shiv Srivastava, Jennifer Cullen, György Petrovics, Graham Casey, Ying Wang, Yao Tettey, Joseph Lachance, Wei Tang, Richard Biritwum, Andrew A. Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Kosj Yamoah, Koveela Govindasami, Anand P. Chokkalingam, Jacob M. Keaton, Jacklyn N. Hellwege, Peter E. Clark, Mohamed Jalloh, Sérigne Maguèye Gueye, Lamine Niang, Olufemi J. Ogunbiyi, Olayiwola Shittu, Olukemi K. Amodu, Akindele O. Adebiyi, Oseremen I. Aisuodionoe-Shadrach, Hafees O. Ajibola, Mustapha A. Jamda, Olabode P. Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua O.D. Abrahams, Halimatou Diop‐Ndiaye, Susan Gundell, Monique J. Roobol, Guido Jenster, Ron HN van Schaik, Jennifer J. Hu, Maureen Sanderson, Linda Kachuri, Rohit Varma, Roberta McKean‐Cowdin, Mina Torres, Michael Preuß, Ruth J. F. Loos, Matthew Zawistowski, Sebastian Zöllner, Zeyun Lu, Stephen K. Van Den Eeden, Douglas F. Easton, Stefan Ambs, Todd L. Edwards, Reedik Mägi, Timothy R. Rebbeck, Lars G. Fritsche, Stephen J. Chanock, Sonja I. Berndt, Fredrik Wiklund, Hidewaki Nakagawa, John S. Witte, J. Michael Gaziano, Amy C. Justice, Nicholas Mancuso, Chikashi Terao, Rosalind A. Eeles, Zsofia Kote‐Jarai, Ravi Madduri, David V. Conti, Christopher A. Haiman · 发表于：Nature Genetics · 年份：2023 · DOI：10.1038/s41588-023-01534-4 · 被引用次数：150 · 研究领域：Genetic Associations and Epidemiology、Prostate Cancer Treatment and Research、Prostate Cancer Diagnosis and Treatment

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.