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

Anqi Wang, Jiayi Shen, Alex A. Rodriguez, Edward J. Saunders, Fei Chen, Rohini Janivara, Burcu F. Darst, Xin Sheng, Yili Xu, Alisha J. Chou, Sara Benlloch, Tokhir Dadaev, Mark N. Brook, Anna Plym, Ali Sahimi, Thomas J. Hoffman, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi FujitaTriin Laisk, Jéssica Figuerêdo, Kenneth Muir, Shuji Ito, Xiaoxi Liu, 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 P. Choudhury, Johanna Schleutker, Teuvo L.J. Tammela, Csilla Sipeky, Anssi Auvinen, Graham G. Giles, Melissa C. Southey, Robert J. MacInnis, Cezary Cybulski, Dominika Wokolorczyk, Jan Lubinski, Christopher T. Rentsch, Kelly Cho, Benjamin H. Mcmahon, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Borge G. Nordestgaard, Sune F. Nielsen, Maren Weischer, Stig E. Bojesen, Andreas Røder, Hein V. Stroomberg, Jyotsna Batra, Suzanne Chambers, Lisa Horvath, Judith A. Clements, Wayne Tilly, Gail P. Risbridger, Henrik Gronberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordstrom, Nora Pashayan, Alison M. Dunning, Maya Ghoussaini, Ruth C. Travis, Tim J. Key, Elio Riboli, Jong Y. Park, Thomas A. Sellers, Hui Yi Lin, Demetrius Albanes, Stephanie Weinstein, Michael B. Cook, Lorelei A. Mucci, Edward Giovannucci, Sara Lindstrom, 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 Stampfer, Alicja Wolk, Niclas Håkansson, Gerald L. Andriole, Robert N. Hoover, Mitchell J. Machiela, Karina Dalsgaard Sørensen, Michael Borre, William J. Blot, Wei Zheng, Edward D. Yeboah, James E. Mensah, Yong Jie Lu, Hong Wei Zhang, Ninghan Feng, Xueying Mao, Yudong Wu, Shan Chao Zhao, Zan Sun, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Catharine M.L. West, Gill Barnett, Christiane Maier, Thomas Schnoeller, Manuel Luedeke, Adam S. Kibel, Bettina F. Drake, Olivier Cussenot, Geraldine Cancel-Tassin, Florence Menegaux, Thérèse Truong, Yves Akoli Koudou, Esther M. John, Eli Marie Grindedal, Lovise Maehle, 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, Ebonee N. Butler, James L. Mohler, Jack A. Taylor, Manolis Kogevinas, Trinidad Dierssen-Sotos, Gemma Castaño-Vinyals, Lisa Cannon-Albright, Craig C. Teerlink, Chad D. Huff, Patrick Pilie, 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 Carpten, Hardev Pandha, Agnieszka Michael, Kim De Ruyck, Gert De Meerleer, Piet Ost, Jianfeng Xu, Azad Razack, Jasmine Lim, Soo Hwang Teo, Lisa F. Newcomb, Daniel W. Lin, Jay H. Fowke, Christine M. Neslund-Dudas, Benjamin A. Rybicki, Marija Gamulin, Davor Lessel, Tomislav Kulis, Nawaid Usmani, Aswin Abraham, Sandeep Singhal, Matthew Parliament, Frank Claessens, Steven Joniau, Thomas Van den Broeck, Manuela Gago-Dominguez, Jose Esteban 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, Gyorgy Petrovics, Graham Casey, Ying Wang, Yao Tettey, Joseph Lachance, Wei Tang, Richard B. 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, Serigne M. Gueye, Lamine Niang, Olufemi Ogunbiyi, Olayiwola Shittu, Olukemi Amodu, Akindele O. Adebiyi, Oseremen I. Aisuodionoe-Shadrach, Hafees O. Ajibola, Mustapha A. Jamda, Olabode P. Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa-Abrahams, Halimatou Diop, Susan M. Gundell, Monique J. Roobol, Guido Jenster, Ron H.N. van Schaik, Jennifer J. Hu, Maureen Sanderson, Linda Kachuri, Rohit Varma, Roberta McKean-Cowdin, Mina Torres, Michael H. 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 Fritsche, Stephen J. Chanock, Sonja I. Berndt, Fredrik Wiklund, Hidewaki Nakagawa, John S. Witte, J. Michael Gaziano, Amy C. Justice, Nick Mancuso, Chikashi Terao, Rosalind A. Eeles, Zsofia Kote-Jarai, Ravi K. Madduri, David V. Conti, Christopher A. Haiman*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2065-2074
Number of pages10
JournalNature Genetics
Volume55
Issue number12
DOIs
Publication statusPublished - Dec 2023

Bibliographical note

Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.

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