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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 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 LJ;
- 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, 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 ML;
- 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 JM;
- 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 HN;
- Hu, Jennifer J;
- Sanderson, Maureen;
- Kachuri, Linda;
- Varma, Rohit;
- McKean-Cowdin, Roberta;
- Torres, Mina;
- Preuss, Michael H;
- Loos, Ruth JF;
- 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
Published Web Location
https://doi.org/10.1038/s41588-023-01534-4Abstract
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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