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

the BioBank Japan Project; Anqi Wang; Jiayi Shen; Alex A. Rodriguez; Edward J. Saunders; Fei Chen; Rohini Janivara; Burcu F. Darst; Xin Sheng; Yili Xu; Alisha J. Chou; Sara Benlloch; Tokhir Dadaev; Mark N. Brook; Anna Plym; Ali Sahimi; Thomas J. Hoffman; Atushi Takahashi; Koichi Matsuda; Yukihide Momozawa; Masashi Fujita; Triin Laisk; Jéssica Figuerêdo; Kenneth Muir; Shuji Ito; Xiaoxi Liu; Yuji Yamanashi; Yoichi Furukawa; Takayuki Morisaki; Yoshinori Murakami; Kaori Muto; Akiko Nagai; Wataru Obara; Ken Yamaji; Kazuhisa Takahashi; Satoshi Asai; Yasuo Takahashi; Takao Suzuki; Nobuaki Sinozaki; Hiroki Yamaguchi; Shiro Minami; Shigeo Murayama; Kozo Yoshimori; Satoshi Nagayama; Daisuke Obata; Masahiko Higashiyama; Akihide Masumoto; Yukihiro Koretsune; Yuji Uchio; Michiaki Kubo; Yoichiro Kamatani; Artitaya Lophatananon; Peggy Wan; Caroline Andrews; Adriana Lori; Parichoy P. Choudhury; Johanna Schleutker; Teuvo L.J. Tammela; Csilla Sipeky; Anssi Auvinen; Graham G. Giles; Melissa C. Southey; Robert J. MacInnis; Cezary Cybulski; Dominika Wokolorczyk; Jan Lubinski; Christopher T. Rentsch; Kelly Cho; Benjamin H. Mcmahon; David E. Neal; Jenny L. Donovan; Freddie C. Hamdy; Richard M. Martin; Borge G. Nordestgaard; Sune F. Nielsen; Maren Weischer; Stig E. Bojesen; Andreas Røder; Hein V. Stroomberg; Jyotsna Batra; Suzanne Chambers; Lisa Horvath; Judith A. Clements; Wayne Tilly; Gail P. Risbridger; Henrik Gronberg; Markus Aly; Robert Szulkin; Martin Eklund; Tobias Nordstrom; Nora Pashayan; Alison M. Dunning; Maya Ghoussaini; Ruth C. Travis; Tim J. Key; Elio Riboli; Jong Y. Park; Thomas A. Sellers; Hui Yi Lin; Demetrius Albanes; Stephanie Weinstein; Michael B. Cook; Lorelei A. Mucci; Edward Giovannucci; Sara Lindstrom; Peter Kraft; David J. Hunter; Kathryn L. Penney; Constance Turman; Catherine M. Tangen; Phyllis J. Goodman; Ian M. Thompson; Robert J. Hamilton; Neil E. Fleshner; Antonio Finelli; Marie Élise Parent; Janet L. Stanford; Elaine A. Ostrander; Stella Koutros; Laura E. Beane Freeman; Meir Stampfer; Alicja Wolk; Niclas Håkansson; Gerald L. Andriole; Robert N. Hoover; Mitchell J. Machiela; Karina Dalsgaard Sørensen; Michael Borre; William J. Blot; Wei Zheng; Edward D. Yeboah; James E. Mensah; Yong Jie Lu; Hong Wei Zhang; Ninghan Feng; Xueying Mao; Yudong Wu; Shan Chao Zhao; Zan Sun; Stephen N. Thibodeau; Shannon K. McDonnell; Daniel J. Schaid; Catharine M.L. West; Gill Barnett; Christiane Maier; Thomas Schnoeller; Manuel Luedeke; Adam S. Kibel; Bettina F. Drake; Olivier Cussenot; Geraldine Cancel-Tassin; Florence Menegaux; Thérèse Truong; Yves Akoli Koudou; Esther M. John; Eli Marie Grindedal; Lovise Maehle; Kay Tee Khaw; Sue A. Ingles; Mariana C. Stern; Ana Vega; Antonio Gómez-Caamaño; Laura Fachal; Barry S. Rosenstein; Sarah L. Kerns; Harry Ostrer; Manuel R. Teixeira; Paula Paulo; Andreia Brandão; Stephen Watya; Alexander Lubwama; Jeannette T. Bensen; Ebonee N. Butler; James L. Mohler; Jack A. Taylor; Manolis Kogevinas; Trinidad Dierssen-Sotos; Gemma Castaño-Vinyals; Lisa Cannon-Albright; Craig C. Teerlink; Chad D. Huff; Patrick Pilie; Yao Yu; Ryan J. Bohlender; Jian Gu; Sara S. Strom; Luc Multigner; Pascal Blanchet; Laurent Brureau; Radka Kaneva; Chavdar Slavov; Vanio Mitev; Robin J. Leach; Hermann Brenner; Xuechen Chen; Bernd Holleczek; Ben Schöttker; Eric A. Klein; Ann W. Hsing; Rick A. Kittles; Adam B. Murphy

doi:10.1038/s41588-023-01534-4

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

the BioBank Japan Project, Anqi Wang, Jiayi Shen, Alex A. Rodriguez, Edward J. Saunders, Fei Chen, Rohini Janivara, Burcu F. Darst, Xin Sheng, Yili Xu, Alisha J. Chou, Sara Benlloch, Tokhir Dadaev, Mark N. Brook, Anna Plym, Ali Sahimi, Thomas J. Hoffman, Atushi Takahashi, Koichi Matsuda, Yukihide MomozawaMasashi Fujita, Triin Laisk, Jéssica Figuerêdo, Kenneth Muir, Shuji Ito, Xiaoxi Liu, Yuji Yamanashi, Yoichi Furukawa, Takayuki Morisaki, Yoshinori Murakami, Kaori Muto, Akiko Nagai, Wataru Obara, Ken Yamaji, Kazuhisa Takahashi, Satoshi Asai, Yasuo Takahashi, Takao Suzuki, Nobuaki Sinozaki, Hiroki Yamaguchi, Shiro Minami, Shigeo Murayama, Kozo Yoshimori, Satoshi Nagayama, Daisuke Obata, Masahiko Higashiyama, Akihide Masumoto, Yukihiro Koretsune, Yuji Uchio, Michiaki Kubo, Yoichiro Kamatani, Artitaya Lophatananon, Peggy Wan, Caroline Andrews, Adriana Lori, Parichoy P. Choudhury, Johanna Schleutker, Teuvo L.J. Tammela, Csilla Sipeky, Anssi Auvinen, Graham G. Giles, Melissa C. Southey, Robert J. MacInnis, Cezary Cybulski, Dominika Wokolorczyk, Jan Lubinski, Christopher T. Rentsch, Kelly Cho, Benjamin H. Mcmahon, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Borge G. Nordestgaard, Sune F. Nielsen, Maren Weischer, Stig E. Bojesen, Andreas Røder, Hein V. Stroomberg, Jyotsna Batra, Suzanne Chambers, Lisa Horvath, Judith A. Clements, Wayne Tilly, Gail P. Risbridger, Henrik Gronberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordstrom, Nora Pashayan, Alison M. Dunning, Maya Ghoussaini, Ruth C. Travis, Tim J. Key, Elio Riboli, Jong Y. Park, Thomas A. Sellers, Hui Yi Lin, Demetrius Albanes, Stephanie Weinstein, Michael B. Cook, Lorelei A. Mucci, Edward Giovannucci, Sara Lindstrom, Peter Kraft, David J. Hunter, Kathryn L. Penney, Constance Turman, Catherine M. Tangen, Phyllis J. Goodman, Ian M. Thompson, Robert J. Hamilton, Neil E. Fleshner, Antonio Finelli, Marie Élise Parent, Janet L. Stanford, Elaine A. Ostrander, Stella Koutros, Laura E. Beane Freeman, Meir Stampfer, Alicja Wolk, Niclas Håkansson, Gerald L. Andriole, Robert N. Hoover, Mitchell J. Machiela, Karina Dalsgaard Sørensen, Michael Borre, William J. Blot, Wei Zheng, Edward D. Yeboah, James E. Mensah, Yong Jie Lu, Hong Wei Zhang, Ninghan Feng, Xueying Mao, Yudong Wu, Shan Chao Zhao, Zan Sun, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Catharine M.L. West, Gill Barnett, Christiane Maier, Thomas Schnoeller, Manuel Luedeke, Adam S. Kibel, Bettina F. Drake, Olivier Cussenot, Geraldine Cancel-Tassin, Florence Menegaux, Thérèse Truong, Yves Akoli Koudou, Esther M. John, Eli Marie Grindedal, Lovise Maehle, Kay Tee Khaw, Sue A. Ingles, Mariana C. Stern, Ana Vega, Antonio Gómez-Caamaño, Laura Fachal, Barry S. Rosenstein, Sarah L. Kerns, Harry Ostrer, Manuel R. Teixeira, Paula Paulo, Andreia Brandão, Stephen Watya, Alexander Lubwama, Jeannette T. Bensen, Ebonee N. Butler, James L. Mohler, Jack A. Taylor, Manolis Kogevinas, Trinidad Dierssen-Sotos, Gemma Castaño-Vinyals, Lisa Cannon-Albright, Craig C. Teerlink, Chad D. Huff, Patrick Pilie, Yao Yu, Ryan J. Bohlender, Jian Gu, Sara S. Strom, Luc Multigner, Pascal Blanchet, Laurent Brureau, Radka Kaneva, Chavdar Slavov, Vanio Mitev, Robin J. Leach, Hermann Brenner, Xuechen Chen, Bernd Holleczek, Ben Schöttker, Eric A. Klein, Ann W. Hsing, Rick A. Kittles, Adam B. Murphy

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

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.

Original language	English
Pages (from-to)	2065-2074
Number of pages	10
Journal	Nature Genetics
Volume	55
Issue number	12
DOIs	https://doi.org/10.1038/s41588-023-01534-4
State	Published - Dec 2023

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10.1038/s41588-023-01534-4

Cite this

the BioBank Japan Project, Wang, A., Shen, J., Rodriguez, A. A., Saunders, E. J., Chen, F., Janivara, R., Darst, B. F., Sheng, X., Xu, Y., Chou, A. J., Benlloch, S., Dadaev, T., Brook, M. N., Plym, A., Sahimi, A., Hoffman, T. J., Takahashi, A., Matsuda, K., ... Murphy, A. B. (2023). Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants. Nature Genetics, 55(12), 2065-2074. https://doi.org/10.1038/s41588-023-01534-4

@article{b7abcb722b9841d394867052657ead8c,

title = "Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants",

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.",

author = "{the BioBank Japan Project} and Anqi Wang and Jiayi Shen and Rodriguez, {Alex A.} and Saunders, {Edward J.} and Fei Chen and Rohini Janivara and Darst, {Burcu F.} and Xin Sheng and Yili Xu and Chou, {Alisha J.} and Sara Benlloch and Tokhir Dadaev and Brook, {Mark N.} and Anna Plym and Ali Sahimi and Hoffman, {Thomas J.} and Atushi Takahashi and Koichi Matsuda and Yukihide Momozawa and Masashi Fujita and Triin Laisk and J{\'e}ssica Figuer{\^e}do and Kenneth Muir and Shuji Ito and Xiaoxi Liu and Yuji Yamanashi and Yoichi Furukawa and Takayuki Morisaki and Yoshinori Murakami and Kaori Muto and Akiko Nagai and Wataru Obara and Ken Yamaji and Kazuhisa Takahashi and Satoshi Asai and Yasuo Takahashi and Takao Suzuki and Nobuaki Sinozaki and Hiroki Yamaguchi and Shiro Minami and Shigeo Murayama and Kozo Yoshimori and Satoshi Nagayama and Daisuke Obata and Masahiko Higashiyama and Akihide Masumoto and Yukihiro Koretsune and Yuji Uchio and Michiaki Kubo and Yoichiro Kamatani and Artitaya Lophatananon and Peggy Wan and Caroline Andrews and Adriana Lori and Choudhury, {Parichoy P.} and Johanna Schleutker and Tammela, {Teuvo L.J.} and Csilla Sipeky and Anssi Auvinen and Giles, {Graham G.} and Southey, {Melissa C.} and MacInnis, {Robert J.} and Cezary Cybulski and Dominika Wokolorczyk and Jan Lubinski and Rentsch, {Christopher T.} and Kelly Cho and Mcmahon, {Benjamin H.} and Neal, {David E.} and Donovan, {Jenny L.} and Hamdy, {Freddie C.} and Martin, {Richard M.} and Nordestgaard, {Borge G.} and Nielsen, {Sune F.} and Maren Weischer and Bojesen, {Stig E.} and Andreas R{\o}der and Stroomberg, {Hein V.} and Jyotsna Batra and Suzanne Chambers and Lisa Horvath and Clements, {Judith A.} and Wayne Tilly and Risbridger, {Gail P.} and Henrik Gronberg and Markus Aly and Robert Szulkin and Martin Eklund and Tobias Nordstrom and Nora Pashayan and Dunning, {Alison M.} and Maya Ghoussaini and Travis, {Ruth C.} and Key, {Tim J.} and Elio Riboli and Park, {Jong Y.} and Sellers, {Thomas A.} and Lin, {Hui Yi} and Demetrius Albanes and Stephanie Weinstein and Cook, {Michael B.} and Mucci, {Lorelei A.} and Edward Giovannucci and Sara Lindstrom and Peter Kraft and Hunter, {David J.} and Penney, {Kathryn L.} and Constance Turman and Tangen, {Catherine M.} and Goodman, {Phyllis J.} and Thompson, {Ian M.} and Hamilton, {Robert J.} and Fleshner, {Neil E.} and Antonio Finelli and Parent, {Marie {\'E}lise} and Stanford, {Janet L.} and Ostrander, {Elaine A.} and Stella Koutros and {Beane Freeman}, {Laura E.} and Meir Stampfer and Alicja Wolk and Niclas H{\aa}kansson and Andriole, {Gerald L.} and Hoover, {Robert N.} and Machiela, {Mitchell J.} and S{\o}rensen, {Karina Dalsgaard} and Michael Borre and Blot, {William J.} and Wei Zheng and Yeboah, {Edward D.} and Mensah, {James E.} and Lu, {Yong Jie} and Zhang, {Hong Wei} and Ninghan Feng and Xueying Mao and Yudong Wu and Zhao, {Shan Chao} and Zan Sun and Thibodeau, {Stephen N.} and McDonnell, {Shannon K.} and Schaid, {Daniel J.} and West, {Catharine M.L.} and Gill Barnett and Christiane Maier and Thomas Schnoeller and Manuel Luedeke and Kibel, {Adam S.} and Drake, {Bettina F.} and Olivier Cussenot and Geraldine Cancel-Tassin and Florence Menegaux and Th{\'e}r{\`e}se Truong and Koudou, {Yves Akoli} and John, {Esther M.} and Grindedal, {Eli Marie} and Lovise Maehle and Khaw, {Kay Tee} and Ingles, {Sue A.} and Stern, {Mariana C.} and Ana Vega and Antonio G{\'o}mez-Caama{\~n}o and Laura Fachal and Rosenstein, {Barry S.} and Kerns, {Sarah L.} and Harry Ostrer and Teixeira, {Manuel R.} and Paula Paulo and Andreia Brand{\~a}o and Stephen Watya and Alexander Lubwama and Bensen, {Jeannette T.} and Butler, {Ebonee N.} and Mohler, {James L.} and Taylor, {Jack A.} and Manolis Kogevinas and Trinidad Dierssen-Sotos and Gemma Casta{\~n}o-Vinyals and Lisa Cannon-Albright and Teerlink, {Craig C.} and Huff, {Chad D.} and Patrick Pilie and Yao Yu and Bohlender, {Ryan J.} and Jian Gu and Strom, {Sara S.} and Luc Multigner and Pascal Blanchet and Laurent Brureau and Radka Kaneva and Chavdar Slavov and Vanio Mitev and Leach, {Robin J.} and Hermann Brenner and Xuechen Chen and Bernd Holleczek and Ben Sch{\"o}ttker and Klein, {Eric A.} and Hsing, {Ann W.} and Kittles, {Rick A.} and Murphy, {Adam B.}",

note = "Publisher Copyright: {\textcopyright} 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2023",

month = dec,

doi = "10.1038/s41588-023-01534-4",

language = "English",

volume = "55",

pages = "2065--2074",

journal = "Nature Genetics",

issn = "1061-4036",

number = "12",

}

the BioBank Japan Project, 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, Yamanashi, Y, Furukawa, Y, Morisaki, T, Murakami, Y, Muto, K, Nagai, A, Obara, W, Yamaji, K, Takahashi, K, Asai, S, Takahashi, Y, Suzuki, T, Sinozaki, N, Yamaguchi, H, Minami, S, Murayama, S, Yoshimori, K, Nagayama, S, Obata, D, Higashiyama, M, Masumoto, A, Koretsune, Y, 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, 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 2023, 'Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants', Nature Genetics, vol. 55, no. 12, pp. 2065-2074. https://doi.org/10.1038/s41588-023-01534-4

TY - JOUR

T1 - Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants

AU - the BioBank Japan Project

AU - Wang, Anqi

AU - Shen, Jiayi

AU - Rodriguez, Alex A.

AU - Saunders, Edward J.

AU - Chen, Fei

AU - Janivara, Rohini

AU - Darst, Burcu F.

AU - Sheng, Xin

AU - Xu, Yili

AU - Chou, Alisha J.

AU - Benlloch, Sara

AU - Dadaev, Tokhir

AU - Brook, Mark N.

AU - Plym, Anna

AU - Sahimi, Ali

AU - Hoffman, Thomas J.

AU - Takahashi, Atushi

AU - Matsuda, Koichi

AU - Momozawa, Yukihide

AU - Fujita, Masashi

AU - Laisk, Triin

AU - Figuerêdo, Jéssica

AU - Muir, Kenneth

AU - Ito, Shuji

AU - Liu, Xiaoxi

AU - Yamanashi, Yuji

AU - Furukawa, Yoichi

AU - Morisaki, Takayuki

AU - Murakami, Yoshinori

AU - Muto, Kaori

AU - Nagai, Akiko

AU - Obara, Wataru

AU - Yamaji, Ken

AU - Takahashi, Kazuhisa

AU - Asai, Satoshi

AU - Takahashi, Yasuo

AU - Suzuki, Takao

AU - Sinozaki, Nobuaki

AU - Yamaguchi, Hiroki

AU - Minami, Shiro

AU - Murayama, Shigeo

AU - Yoshimori, Kozo

AU - Nagayama, Satoshi

AU - Obata, Daisuke

AU - Higashiyama, Masahiko

AU - Masumoto, Akihide

AU - Koretsune, Yukihiro

AU - Uchio, Yuji

AU - Kubo, Michiaki

AU - Kamatani, Yoichiro

AU - Lophatananon, Artitaya

AU - Wan, Peggy

AU - Andrews, Caroline

AU - Lori, Adriana

AU - Choudhury, Parichoy P.

AU - Schleutker, Johanna

AU - Tammela, Teuvo L.J.

AU - Sipeky, Csilla

AU - Auvinen, Anssi

AU - Giles, Graham G.

AU - Southey, Melissa C.

AU - MacInnis, Robert J.

AU - Cybulski, Cezary

AU - Wokolorczyk, Dominika

AU - Lubinski, Jan

AU - Rentsch, Christopher T.

AU - Cho, Kelly

AU - Mcmahon, Benjamin H.

AU - Neal, David E.

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Martin, Richard M.

AU - Nordestgaard, Borge G.

AU - Nielsen, Sune F.

AU - Weischer, Maren

AU - Bojesen, Stig E.

AU - Røder, Andreas

AU - Stroomberg, Hein V.

AU - Batra, Jyotsna

AU - Chambers, Suzanne

AU - Horvath, Lisa

AU - Clements, Judith A.

AU - Tilly, Wayne

AU - Risbridger, Gail P.

AU - Gronberg, Henrik

AU - Aly, Markus

AU - Szulkin, Robert

AU - Eklund, Martin

AU - Nordstrom, Tobias

AU - Pashayan, Nora

AU - Dunning, Alison M.

AU - Ghoussaini, Maya

AU - Travis, Ruth C.

AU - Key, Tim J.

AU - Riboli, Elio

AU - Park, Jong Y.

AU - Sellers, Thomas A.

AU - Lin, Hui Yi

AU - Albanes, Demetrius

AU - Weinstein, Stephanie

AU - Cook, Michael B.

AU - Mucci, Lorelei A.

AU - Giovannucci, Edward

AU - Lindstrom, Sara

AU - Kraft, Peter

AU - Hunter, David J.

AU - Penney, Kathryn L.

AU - Turman, Constance

AU - Tangen, Catherine M.

AU - Goodman, Phyllis J.

AU - Thompson, Ian M.

AU - Hamilton, Robert J.

AU - Fleshner, Neil E.

AU - Finelli, Antonio

AU - Parent, Marie Élise

AU - Stanford, Janet L.

AU - Ostrander, Elaine A.

AU - Koutros, Stella

AU - Beane Freeman, Laura E.

AU - Stampfer, Meir

AU - Wolk, Alicja

AU - Håkansson, Niclas

AU - Andriole, Gerald L.

AU - Hoover, Robert N.

AU - Machiela, Mitchell J.

AU - Sørensen, Karina Dalsgaard

AU - Borre, Michael

AU - Blot, William J.

AU - Zheng, Wei

AU - Yeboah, Edward D.

AU - Mensah, James E.

AU - Lu, Yong Jie

AU - Zhang, Hong Wei

AU - Feng, Ninghan

AU - Mao, Xueying

AU - Wu, Yudong

AU - Zhao, Shan Chao

AU - Sun, Zan

AU - Thibodeau, Stephen N.

AU - McDonnell, Shannon K.

AU - Schaid, Daniel J.

AU - West, Catharine M.L.

AU - Barnett, Gill

AU - Maier, Christiane

AU - Schnoeller, Thomas

AU - Luedeke, Manuel

AU - Kibel, Adam S.

AU - Drake, Bettina F.

AU - Cussenot, Olivier

AU - Cancel-Tassin, Geraldine

AU - Menegaux, Florence

AU - Truong, Thérèse

AU - Koudou, Yves Akoli

AU - John, Esther M.

AU - Grindedal, Eli Marie

AU - Maehle, Lovise

AU - Khaw, Kay Tee

AU - Ingles, Sue A.

AU - Stern, Mariana C.

AU - Vega, Ana

AU - Gómez-Caamaño, Antonio

AU - Fachal, Laura

AU - Rosenstein, Barry S.

AU - Kerns, Sarah L.

AU - Ostrer, Harry

AU - Teixeira, Manuel R.

AU - Paulo, Paula

AU - Brandão, Andreia

AU - Watya, Stephen

AU - Lubwama, Alexander

AU - Bensen, Jeannette T.

AU - Butler, Ebonee N.

AU - Mohler, James L.

AU - Taylor, Jack A.

AU - Kogevinas, Manolis

AU - Dierssen-Sotos, Trinidad

AU - Castaño-Vinyals, Gemma

AU - Cannon-Albright, Lisa

AU - Teerlink, Craig C.

AU - Huff, Chad D.

AU - Pilie, Patrick

AU - Yu, Yao

AU - Bohlender, Ryan J.

AU - Gu, Jian

AU - Strom, Sara S.

AU - Multigner, Luc

AU - Blanchet, Pascal

AU - Brureau, Laurent

AU - Kaneva, Radka

AU - Slavov, Chavdar

AU - Mitev, Vanio

AU - Leach, Robin J.

AU - Brenner, Hermann

AU - Chen, Xuechen

AU - Holleczek, Bernd

AU - Schöttker, Ben

AU - Klein, Eric A.

AU - Hsing, Ann W.

AU - Kittles, Rick A.

AU - Murphy, Adam B.

PY - 2023/12

Y1 - 2023/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85176259299&partnerID=8YFLogxK

U2 - 10.1038/s41588-023-01534-4

DO - 10.1038/s41588-023-01534-4

M3 - Article

C2 - 37945903

AN - SCOPUS:85176259299

SN - 1061-4036

VL - 55

SP - 2065

EP - 2074

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

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

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