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

Wang, AnqiORCID logo; Shen, JiayiORCID logo; Rodriguez, Alex A; Saunders, Edward J; Chen, Fei; Janivara, RohiniORCID logo; Darst, Burcu FORCID logo; Sheng, Xin; Xu, YiliORCID logo; Chou, Alisha JORCID logo; +282 more...Benlloch, Sara; Dadaev, TokhirORCID logo; Brook, Mark NORCID logo; Plym, Anna; Sahimi, Ali; Hoffman, Thomas JORCID logo; Takahashi, AtushiORCID logo; Matsuda, KoichiORCID logo; Momozawa, YukihideORCID logo; Fujita, MasashiORCID logo; Laisk, TriinORCID logo; Figuerêdo, Jéssica; Muir, KennethORCID logo; Ito, Shuji; Liu, Xiaoxi; Biobank Japan Project; Uchio, YujiORCID logo; Kubo, Michiaki; Kamatani, YoichiroORCID logo; Lophatananon, Artitaya; Wan, Peggy; Andrews, Caroline; Lori, Adriana; Choudhury, Parichoy P; Schleutker, JohannaORCID logo; Tammela, Teuvo LJ; Sipeky, CsillaORCID logo; Auvinen, AnssiORCID logo; Giles, Graham GORCID logo; Southey, Melissa CORCID logo; MacInnis, Robert J; Cybulski, Cezary; Wokolorczyk, Dominika; Lubinski, Jan; Rentsch, Christopher TORCID logo; Cho, Kelly; Mcmahon, Benjamin H; Neal, David E; Donovan, Jenny L; Hamdy, Freddie C; Martin, Richard MORCID logo; Nordestgaard, Borge GORCID logo; Nielsen, Sune F; Weischer, Maren; Bojesen, Stig EORCID logo; Røder, AndreasORCID logo; Stroomberg, Hein VORCID logo; Batra, JyotsnaORCID logo; Chambers, Suzanne; Horvath, LisaORCID logo; Clements, Judith AORCID logo; Tilly, WayneORCID logo; Risbridger, Gail PORCID logo; Gronberg, HenrikORCID logo; Aly, MarkusORCID logo; Szulkin, Robert; Eklund, MartinORCID logo; Nordstrom, TobiasORCID logo; Pashayan, NoraORCID logo; Dunning, Alison MORCID logo; Ghoussaini, MayaORCID logo; Travis, Ruth CORCID logo; Key, Tim J; Riboli, ElioORCID logo; Park, Jong YORCID logo; Sellers, Thomas A; Lin, Hui-Yi; Albanes, DemetriusORCID logo; Weinstein, StephanieORCID logo; Cook, Michael B; Mucci, Lorelei A; Giovannucci, Edward; Lindstrom, Sara; Kraft, PeterORCID logo; 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-ÉliseORCID logo; Stanford, Janet L; Ostrander, Elaine AORCID logo; Koutros, Stella; Beane Freeman, Laura E; Stampfer, Meir; Wolk, AlicjaORCID logo; Håkansson, NiclasORCID logo; Andriole, Gerald L; Hoover, Robert N; Machiela, Mitchell JORCID logo; Sørensen, Karina DalsgaardORCID logo; Borre, Michael; Blot, William J; Zheng, WeiORCID logo; Yeboah, Edward D; Mensah, James EORCID logo; Lu, Yong-JieORCID logo; Zhang, Hong-Wei; Feng, Ninghan; Mao, Xueying; Wu, Yudong; Zhao, Shan-ChaoORCID logo; Sun, Zan; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; West, Catharine MLORCID logo; Barnett, Gill; Maier, Christiane; Schnoeller, Thomas; Luedeke, Manuel; Kibel, Adam S; Drake, Bettina F; Cussenot, Olivier; Cancel-Tassin, GeraldineORCID logo; Menegaux, Florence; Truong, ThérèseORCID logo; Koudou, Yves Akoli; John, Esther M; Grindedal, Eli Marie; Maehle, Lovise; Khaw, Kay-Tee; Ingles, Sue A; Stern, Mariana C; Vega, AnaORCID logo; Gómez-Caamaño, AntonioORCID logo; Fachal, Laura; Rosenstein, Barry S; Kerns, Sarah L; Ostrer, Harry; Teixeira, Manuel RORCID logo; Paulo, Paula; Brandão, AndreiaORCID logo; Watya, Stephen; Lubwama, Alexander; Bensen, Jeannette T; Butler, Ebonee N; Mohler, James LORCID logo; Taylor, Jack AORCID logo; Kogevinas, Manolis; Dierssen-Sotos, Trinidad; Castaño-Vinyals, GemmaORCID logo; Cannon-Albright, LisaORCID logo; Teerlink, Craig C; Huff, Chad D; Pilie, Patrick; Yu, YaoORCID logo; Bohlender, Ryan JORCID logo; Gu, JianORCID logo; Strom, Sara S; Multigner, LucORCID logo; Blanchet, Pascal; Brureau, Laurent; Kaneva, Radka; Slavov, Chavdar; Mitev, Vanio; Leach, Robin J; Brenner, HermannORCID logo; Chen, Xuechen; Holleczek, Bernd; Schöttker, Ben; Klein, Eric AORCID logo; Hsing, Ann W; Kittles, Rick A; Murphy, Adam BORCID logo; Logothetis, Christopher JORCID logo; Kim, Jeri; Neuhausen, Susan LORCID logo; Steele, Linda; Ding, Yuan Chun; Isaacs, William B; Nemesure, Barbara; Hennis, Anselm JM; Carpten, John; Pandha, Hardev; Michael, AgnieszkaORCID logo; De Ruyck, Kim; De Meerleer, Gert; Ost, PietORCID logo; Xu, JianfengORCID logo; Razack, Azad; Lim, Jasmine; Teo, Soo-HwangORCID logo; Newcomb, Lisa F; Lin, Daniel W; Fowke, Jay H; Neslund-Dudas, Christine M; Rybicki, Benjamin A; Gamulin, MarijaORCID logo; Lessel, DavorORCID logo; Kulis, TomislavORCID logo; Usmani, Nawaid; Abraham, Aswin; Singhal, Sandeep; Parliament, Matthew; Claessens, Frank; Joniau, StevenORCID logo; Van den Broeck, Thomas; Gago-Dominguez, Manuela; Castelao, Jose Esteban; Martinez, Maria Elena; Larkin, Samantha; Townsend, Paul A; Aukim-Hastie, Claire; Bush, William SORCID logo; Aldrich, Melinda CORCID logo; Crawford, Dana CORCID logo; Srivastava, Shiv; Cullen, Jennifer; Petrovics, GyorgyORCID logo; Casey, Graham; Wang, YingORCID logo; Tettey, Yao; Lachance, JosephORCID logo; Tang, WeiORCID logo; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Yamoah, KosjORCID logo; Govindasami, Koveela; Chokkalingam, Anand P; Keaton, Jacob M; Hellwege, Jacklyn N; Clark, Peter E; Jalloh, MohamedORCID logo; Gueye, Serigne M; Niang, Lamine; Ogunbiyi, Olufemi; Shittu, Olayiwola; Amodu, Olukemi; Adebiyi, Akindele OORCID logo; Aisuodionoe-Shadrach, Oseremen I; Ajibola, Hafees O; Jamda, Mustapha A; Oluwole, Olabode P; Nwegbu, Maxwell; Adusei, Ben; Mante, SunnyORCID logo; Darkwa-Abrahams, Afua; Diop, Halimatou; Gundell, Susan M; Roobol, Monique JORCID logo; Jenster, GuidoORCID logo; van Schaik, Ron HN; Hu, Jennifer JORCID logo; Sanderson, Maureen; Kachuri, LindaORCID logo; Varma, Rohit; McKean-Cowdin, Roberta; Torres, Mina; Preuss, Michael HORCID logo; Loos, Ruth JFORCID logo; Zawistowski, MatthewORCID logo; Zöllner, SebastianORCID logo; Lu, ZeyunORCID logo; Van Den Eeden, Stephen KORCID logo; Easton, Douglas FORCID logo; Ambs, StefanORCID logo; Edwards, Todd LORCID logo; Mägi, ReedikORCID logo; Rebbeck, Timothy RORCID logo; Fritsche, LarsORCID logo; Chanock, Stephen JORCID logo; Berndt, Sonja I; Wiklund, FredrikORCID logo; Nakagawa, HidewakiORCID logo; Witte, John SORCID logo; Gaziano, J Michael; Justice, Amy CORCID logo; Mancuso, NickORCID logo; Terao, ChikashiORCID logo; Eeles, Rosalind AORCID logo; Kote-Jarai, ZsofiaORCID logo; Madduri, Ravi KORCID logo; Conti, David VORCID logo; and Haiman, Christopher AORCID logo (2023) Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants. Nature genetics, 55 (12). pp. 2065-2074. ISSN 1061-4036 DOI: 10.1038/s41588-023-01534-4
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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.


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This is an author accepted manuscript version of an article accepted for publication, and following peer review. Please be aware that minor differences may exist between this version and the final version if you wish to cite from it.
Available under Creative Commons: Attribution-NonCommercial-No Derivative Works 3.0

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