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

Wang, A Shen, J Rodriguez, AA Saunders, EJ Chen, F Janivara, R Darst, BF Sheng, X Xu, Y Chou, AJ Benlloch, S Dadaev, T Brook, MN Plym, A Sahimi, A Hoffman, TJ Takahashi, A Matsuda, K Momozawa, Y Fujita, M Laisk, T Figuerêdo, J Muir, K Ito, S Liu, X Biobank Japan Project, Uchio, Y Kubo, M Kamatani, Y Lophatananon, A Wan, P Andrews, C Lori, A Choudhury, PP Schleutker, J Tammela, TLJ Sipeky, C Auvinen, A Giles, GG Southey, MC MacInnis, RJ Cybulski, C Wokolorczyk, D Lubinski, J Rentsch, CT Cho, K Mcmahon, BH Neal, DE Donovan, JL Hamdy, FC Martin, RM Nordestgaard, BG Nielsen, SF Weischer, M Bojesen, SE Røder, A Stroomberg, HV Batra, J Chambers, S ORCID badge Horvath, L Clements, JA Tilly, W Risbridger, GP Gronberg, H Aly, M Szulkin, R Eklund, M Nordstrom, T Pashayan, N Dunning, AM Ghoussaini, M Travis, RC Key, TJ Riboli, E Park, JY Sellers, TA Lin, H-Y Albanes, D Weinstein, S Cook, MB Mucci, LA Giovannucci, E Lindstrom, S Kraft, P Hunter, DJ Penney, KL Turman, C Tangen, CM Goodman, PJ Thompson, IM Hamilton, RJ Fleshner, NE Finelli, A Parent, M-É Stanford, JL Ostrander, EA Koutros, S Beane Freeman, LE Stampfer, M Wolk, A Håkansson, N Andriole, GL Hoover, RN Machiela, MJ Sørensen, KD Borre, M Blot, WJ Zheng, W Yeboah, ED Mensah, JE Lu, Y-J Zhang, H-W Feng, N Mao, X Wu, Y Zhao, S-C Sun, Z Thibodeau, SN McDonnell, SK Schaid, DJ West, CML Barnett, G Maier, C Schnoeller, T Luedeke, M Kibel, AS Drake, BF Cussenot, O Cancel-Tassin, G Menegaux, F Truong, T Koudou, YA John, EM Grindedal, EM Maehle, L Khaw, K-T Ingles, SA Stern, MC Vega, A Gómez-Caamaño, A Fachal, L Rosenstein, BS Kerns, SL Ostrer, H Teixeira, MR Paulo, P Brandão, A Watya, S Lubwama, A Bensen, JT Butler, EN Mohler, JL Taylor, JA Kogevinas, M Dierssen-Sotos, T Castaño-Vinyals, G Cannon-Albright, L Teerlink, CC Huff, CD Pilie, P Yu, Y Bohlender, RJ Gu, J Strom, SS Multigner, L Blanchet, P Brureau, L Kaneva, R Slavov, C Mitev, V Leach, RJ Brenner, H Chen, X Holleczek, B Schöttker, B Klein, EA Hsing, AW Kittles, RA Murphy, AB Logothetis, CJ Kim, J Neuhausen, SL Steele, L Ding, YC Isaacs, WB Nemesure, B Hennis, AJM Carpten, J Pandha, H Michael, A De Ruyck, K De Meerleer, G Ost, P Xu, J Razack, A Lim, J Teo, S-H Newcomb, LF Lin, DW Fowke, JH Neslund-Dudas, CM Rybicki, BA Gamulin, M Lessel, D Kulis, T Usmani, N Abraham, A Singhal, S Parliament, M Claessens, F Joniau, S Van den Broeck, T Gago-Dominguez, M Castelao, JE Martinez, ME Larkin, S Townsend, PA Aukim-Hastie, C Bush, WS Aldrich, MC Crawford, DC Srivastava, S Cullen, J Petrovics, G Casey, G Wang, Y Tettey, Y Lachance, J Tang, W Biritwum, RB Adjei, AA Tay, E Truelove, A Niwa, S Yamoah, K Govindasami, K Chokkalingam, AP Keaton, JM Hellwege, JN Clark, PE Jalloh, M Gueye, SM Niang, L Ogunbiyi, O Shittu, O Amodu, O Adebiyi, AO Aisuodionoe-Shadrach, OI Ajibola, HO Jamda, MA Oluwole, OP Nwegbu, M Adusei, B Mante, S Darkwa-Abrahams, A Diop, H Gundell, SM Roobol, MJ Jenster, G van Schaik, RHN Hu, JJ Sanderson, M Kachuri, L Varma, R McKean-Cowdin, R Torres, M Preuss, MH Loos, RJF Zawistowski, M Zöllner, S Lu, Z Van Den Eeden, SK Easton, DF Ambs, S Edwards, TL Mägi, R Rebbeck, TR Fritsche, L Chanock, SJ Berndt, SI Wiklund, F Nakagawa, H Witte, JS Gaziano, JM Justice, AC Mancuso, N Terao, C Eeles, RA Kote-Jarai, Z Madduri, RK Conti, DV Haiman, CA
Publisher:
Springer Nature
Publication Type:
Journal Article
Citation:
Nat Genet, 2023, pp. 1-10
Issue Date:
2023-11-09
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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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