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