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; Figuer&#234;do, J; Muir, K; Ito, S; Liu, X; The 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; R&#248;der, A; Stroomberg, HV; Batra, J; Chambers, S; 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, HY; 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, Jr; Hamilton, RJ; Fleshner, NE; Finelli, A; Parent, M&#201;; Stanford, JL; Ostrander, EA; Koutros, S; Beane Freeman, LE; Stampfer, M; Wolk, A; H&#229;kansson, N; Andriole, GL; Hoover, RN; Machiela, MJ; S&#248;rensen, KD; Borre, M; Blot, WJ; Zheng, W; Yeboah, ED; Mensah, JE; Lu, YJ; Zhang, HW; Feng, N; Mao, X; Wu, Y; Zhao, SC; 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, KT; Ingles, SA; Stern, MC; Vega, A; G&#243;mez-Caama&#241;o, A; Fachal, L; Rosenstein, BS; Kerns, SL; Ostrer, H; Teixeira, MR; Paulo, P; Brand&#227;o, A; Watya, S; Lubwama, A; Bensen, JT; Butler, EN; Mohler, JL; Taylor, JA; Kogevinas, M; Dierssen-Sotos, T; Casta&#241;o-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; Sch&#246;ttker, 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, SH; 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; Z&#246;llner, S; Lu, Z; Van Den Eeden, SK; Easton, DF; Ambs, S; Edwards, TL; M&#228;gi, 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

Author(s): 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; The 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; 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, HY; 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, Jr; Hamilton, RJ; Fleshner, NE; Finelli, A; Parent, MÉ; 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, YJ; Zhang, HW; Feng, N; Mao, X; Wu, Y; Zhao, SC; 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, KT; 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, SH; 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;
Details: Publication Year 2023-12,Volume 55,Issue #12,Page 2065-2074
Journal Title: Nature Genetics
Publication Type: Research article
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.
Publisher: Springer Nature
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1038/s41588-023-01534-4
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-01-23 03:52:03

Last Modified: 2024-07-30 02:08:41