Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.
Journal: Nature Genetics
Published:
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.
Authors
Anqi Wang, Jiayi Shen, Alex Rodriguez, Edward Saunders, Fei Chen, Rohini Janivara, Burcu Darst, Xin Sheng, Yili Xu, Alisha Chou, Sara Benlloch, Tokhir Dadaev, Mark Brook, Anna Plym, Ali Sahimi, Thomas Hoffman, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi Fujita, Triin Laisk, Jéssica Figuerêdo, Kenneth Muir, Shuji Ito, Xiaoxi Liu, Michiaki Kubo, Yoichiro Kamatani, Artitaya Lophatananon, Peggy Wan, Caroline Andrews, Adriana Lori, Parichoy Choudhury, Johanna Schleutker, Teuvo L Tammela, Csilla Sipeky, Anssi Auvinen, Graham Giles, Melissa Southey, Robert Macinnis, Cezary Cybulski, Dominika Wokolorczyk, Jan Lubinski, Christopher Rentsch, Kelly Cho, Benjamin Mcmahon, David Neal, Jenny Donovan, Freddie Hamdy, Richard Martin, Borge Nordestgaard, Sune Nielsen, Maren Weischer, Stig Bojesen, Andreas Røder, Hein Stroomberg, Jyotsna Batra, Suzanne Chambers, Lisa Horvath, Judith Clements, Wayne Tilly, Gail Risbridger, Henrik Gronberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordstrom, Nora Pashayan, Alison Dunning, Maya Ghoussaini, Ruth Travis, Tim Key, Elio Riboli, Jong Park, Thomas Sellers, Hui-yi Lin, Demetrius Albanes, Stephanie Weinstein, Michael Cook, Lorelei Mucci, Edward Giovannucci, Sara Lindstrom, Peter Kraft, David Hunter, Kathryn Penney, Constance Turman, Catherine Tangen, Phyllis Goodman, Ian Thompson, Robert Hamilton, Neil Fleshner, Antonio Finelli, Marie-élise Parent, Janet Stanford, Elaine Ostrander, Stella Koutros, Laura Beane Freeman, Meir Stampfer, Alicja Wolk, Niclas Håkansson, Gerald Andriole, Robert Hoover, Mitchell Machiela, Karina Sørensen, Michael Borre, William Blot, Wei Zheng, Edward Yeboah, James Mensah, Yong-jie Lu, Hong-wei Zhang, Ninghan Feng, Xueying Mao, Yudong Wu, Shan-chao Zhao, Zan Sun, Stephen Thibodeau, Shannon Mcdonnell, Daniel Schaid, Catharine M West, Gill Barnett, Christiane Maier, Thomas Schnoeller, Manuel Luedeke, Adam Kibel, Bettina Drake, Olivier Cussenot, Geraldine Cancel Tassin, Florence Menegaux, Thérèse Truong, Yves Koudou, Esther John, Eli Grindedal, Lovise Maehle, Kay-tee Khaw, Sue Ingles, Mariana Stern, Ana Vega, Antonio Gómez Caamaño, Laura Fachal, Barry Rosenstein, Sarah Kerns, Harry Ostrer, Manuel Teixeira, Paula Paulo, Andreia Brandão, Stephen Watya, Alexander Lubwama, Jeannette Bensen, Ebonee Butler, James Mohler, Jack Taylor, Manolis Kogevinas, Trinidad Dierssen Sotos, Gemma Castaño Vinyals, Lisa Cannon Albright, Craig Teerlink, Chad Huff, Patrick Pilie, Yao Yu, Ryan Bohlender, Jian Gu, Sara Strom, Luc Multigner, Pascal Blanchet, Laurent Brureau, Radka Kaneva, Chavdar Slavov, Vanio Mitev, Robin Leach, Hermann Brenner, Xuechen Chen, Bernd Holleczek, Ben Schöttker, Eric Klein, Ann Hsing, Rick Kittles, Adam Murphy, Christopher Logothetis, Jeri Kim, Susan Neuhausen, Linda Steele, Yuan Ding, William Isaacs, Barbara Nemesure, Anselm J 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 Newcomb, Daniel Lin, Jay Fowke, Christine Neslund Dudas, Benjamin 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 Castelao, Maria Martinez, Samantha Larkin, Paul Townsend, Claire Aukim Hastie, William Bush, Melinda Aldrich, Dana Crawford, Shiv Srivastava, Jennifer Cullen, Gyorgy Petrovics, Graham Casey, Ying Wang, Yao Tettey, Joseph Lachance, Wei Tang, Richard Biritwum, Andrew Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Kosj Yamoah, Koveela Govindasami, Anand Chokkalingam, Jacob Keaton, Jacklyn Hellwege, Peter Clark, Mohamed Jalloh, Serigne Gueye, Lamine Niang, Olufemi Ogunbiyi, Olayiwola Shittu, Olukemi Amodu, Akindele Adebiyi, Oseremen Aisuodionoe Shadrach, Hafees Ajibola, Mustapha Jamda, Olabode Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa Abrahams, Halimatou Diop, Susan Gundell, Monique Roobol, Guido Jenster, Ron H Van Schaik, Jennifer Hu, Maureen Sanderson, Linda Kachuri, Rohit Varma, Roberta Mckean Cowdin, Mina Torres, Michael Preuss, Ruth J Loos, Matthew Zawistowski, Sebastian Zöllner, Zeyun Lu, Stephen Van Den Eeden, Douglas Easton, Stefan Ambs, Todd Edwards, Reedik Mägi, Timothy Rebbeck, Lars Fritsche, Stephen Chanock, Sonja Berndt, Fredrik Wiklund, Hidewaki Nakagawa, John Witte, J Gaziano, Amy Justice, Nick Mancuso, Chikashi Terao, Rosalind Eeles, Zsofia Kote Jarai, Ravi Madduri, David Conti, Christopher Haiman
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