Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

David V. Conti; Burcu F. Darst; Lilit C. Moss; Edward J. Saunders; Xin Sheng; Alisha Chou; Fredrick R. Schumacher; Ali Amin Al Olama; Sara Benlloch; Tokhir Dadaev; Mark N. Brook; Ali Sahimi; Thomas J. Hoffmann; Atushi Takahashi; Koichi Matsuda; Yukihide Momozawa; Masashi Fujita; Kenneth Muir; Artitaya Lophatananon; Peggy Wan; Loic Le Marchand; Lynne R. Wilkens; Victoria L. Stevens; Susan M. Gapstur; Brian D. Carter; Johanna Schleutker; Teuvo L.J. Tammela; Csilla Sipeky; Anssi Auvinen; Graham G. Giles; Melissa C. Southey; Robert J. MacInnis; Cezary Cybulski; Dominika Wokołorczyk; Jan Lubiński; David E. Neal; Jenny L. Donovan; Freddie C. Hamdy; Richard M. Martin; Børge G. Nordestgaard; Sune F. Nielsen; Maren Weischer; Stig E. Bojesen; Martin Andreas Røder; Peter Iversen; Jyotsna Batra; Suzanne Chambers; Leire Moya; Lisa Horvath; Judith A. Clements; Wayne Tilley; Gail P. Risbridger; Henrik Gronberg; Markus Aly; Robert Szulkin; Martin Eklund; Tobias Nordström; 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 J. Weinstein; 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; Milan S. Geybels; 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; Neil Burnet; Gill Barnett; Christiane Maier; Thomas Schnoeller; Manuel Luedeke; Adam S. Kibel; Bettina F. Drake; Olivier Cussenot; Géraldine 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; Elizabeth T.H. Fontham; James Mohler; Jack A. Taylor; Manolis Kogevinas; Javier Llorca; Gemma Castaño-Vinyals; Lisa Cannon-Albright; Craig C. Teerlink; Chad D. Huff; Sara S. Strom; Luc Multigner; Pascal Blanchet; Laurent Brureau; Radka Kaneva; Chavdar Slavov; Vanio Mitev; Robin J. Leach; Brandi Weaver; Hermann Brenner; Katarina Cuk; Bernd Holleczek; Kai Uwe Saum; Eric A. Klein; Ann W. Hsing; Rick A. Kittles; Adam B. Murphy; Christopher J. Logothetis; Jeri Kim; Susan L. Neuhausen; Linda Steele; Yuan Chun Ding; William B. Isaacs; Barbara Nemesure; Anselm J.M. Hennis; John Carpten; Hardev Pandha; Agnieszka Michael; Kim De Ruyck; Gert De Meerleer; Piet Ost; Jianfeng Xu; Azad Razack; Jasmine Lim; Soo Hwang Teo; Lisa F. Newcomb; Daniel W. Lin; Jay H. Fowke; Christine Neslund-Dudas; Benjamin A. Rybicki; Marija Gamulin; Davor Lessel; Tomislav Kulis; Nawaid Usmani; Sandeep Singhal; Matthew Parliament; Frank Claessens; Steven Joniau; Thomas Van den Broeck; Manuela Gago-Dominguez; Jose Esteban Castelao; Maria Elena Martinez; Samantha Larkin; Paul A. Townsend; Claire Aukim-Hastie; William S. Bush; Melinda C. Aldrich; Dana C. Crawford; Shiv Srivastava; Jennifer C. Cullen; Gyorgy Petrovics; Graham Casey; Monique J. Roobol; Guido Jenster; Ron H.N. van Schaik; Jennifer J. Hu; Maureen Sanderson; Rohit Varma; Roberta McKean-Cowdin; Mina Torres; Nicholas Mancuso; Sonja I. Berndt; Stephen K. Van Den Eeden; Douglas F. Easton; Stephen J. Chanock; Michael B. Cook; Fredrik Wiklund; Hidewaki Nakagawa; John S. Witte; Rosalind A. Eeles; Zsofia Kote-Jarai; Christopher A. Haiman

doi:10.1038/s41588-020-00748-0

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

David V. Conti, Burcu F. Darst, Lilit C. Moss, Edward J. Saunders, Xin Sheng, Alisha Chou, Fredrick R. Schumacher, Ali Amin Al Olama, Sara Benlloch, Tokhir Dadaev, Mark N. Brook, Ali Sahimi, Thomas J. Hoffmann, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi Fujita, Kenneth Muir, Artitaya Lophatananon, Peggy WanLoic Le Marchand, Lynne R. Wilkens, Victoria L. Stevens, Susan M. Gapstur, Brian D. Carter, Johanna Schleutker, Teuvo L.J. Tammela, Csilla Sipeky, Anssi Auvinen, Graham G. Giles, Melissa C. Southey, Robert J. MacInnis, Cezary Cybulski, Dominika Wokołorczyk, Jan Lubiński, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Børge G. Nordestgaard, Sune F. Nielsen, Maren Weischer, Stig E. Bojesen, Martin Andreas Røder, Peter Iversen, Jyotsna Batra, Suzanne Chambers, Leire Moya, Lisa Horvath, Judith A. Clements, Wayne Tilley, Gail P. Risbridger, Henrik Gronberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordström, 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 J. Weinstein, 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, Milan S. Geybels, 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, Neil Burnet, Gill Barnett, Christiane Maier, Thomas Schnoeller, Manuel Luedeke, Adam S. Kibel, Bettina F. Drake, Olivier Cussenot, Géraldine 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, Elizabeth T.H. Fontham, James Mohler, Jack A. Taylor, Manolis Kogevinas, Javier Llorca, Gemma Castaño-Vinyals, Lisa Cannon-Albright, Craig C. Teerlink, Chad D. Huff, Sara S. Strom, Luc Multigner, Pascal Blanchet, Laurent Brureau, Radka Kaneva, Chavdar Slavov, Vanio Mitev, Robin J. Leach, Brandi Weaver, Hermann Brenner, Katarina Cuk, Bernd Holleczek, Kai Uwe Saum, Eric A. Klein, Ann W. Hsing, Rick A. Kittles, Adam B. Murphy, Christopher J. Logothetis, Jeri Kim, Susan L. Neuhausen, Linda Steele, Yuan Chun Ding, William B. Isaacs, Barbara Nemesure, Anselm J.M. Hennis, John Carpten, Hardev Pandha, Agnieszka Michael, Kim De Ruyck, Gert De Meerleer, Piet Ost, Jianfeng Xu, Azad Razack, Jasmine Lim, Soo Hwang Teo, Lisa F. Newcomb, Daniel W. Lin, Jay H. Fowke, Christine Neslund-Dudas, Benjamin A. Rybicki, Marija Gamulin, Davor Lessel, Tomislav Kulis, Nawaid Usmani, Sandeep Singhal, Matthew Parliament, Frank Claessens, Steven Joniau, Thomas Van den Broeck, Manuela Gago-Dominguez, Jose Esteban Castelao, Maria Elena Martinez, Samantha Larkin, Paul A. Townsend, Claire Aukim-Hastie, William S. Bush, Melinda C. Aldrich, Dana C. Crawford, Shiv Srivastava, Jennifer C. Cullen, Gyorgy Petrovics, Graham Casey, Monique J. Roobol, Guido Jenster, Ron H.N. van Schaik, Jennifer J. Hu, Maureen Sanderson, Rohit Varma, Roberta McKean-Cowdin, Mina Torres, Nicholas Mancuso, Sonja I. Berndt, Stephen K. Van Den Eeden, Douglas F. Easton, Stephen J. Chanock, Michael B. Cook, Fredrik Wiklund, Hidewaki Nakagawa, John S. Witte, Rosalind A. Eeles, Zsofia Kote-Jarai, Christopher A. Haiman

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

204 Scopus citations

Abstract

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84–5.29) for men of European ancestry to 3.74 (95% CI, 3.36–4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14–2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71–0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Original language	English (US)
Pages (from-to)	65-75
Number of pages	11
Journal	Nature Genetics
Volume	53
Issue number	1
DOIs	https://doi.org/10.1038/s41588-020-00748-0
State	Published - Jan 2021

ASJC Scopus subject areas

Genetics

MD Anderson CCSG core facilities

Tissue Biospecimen and Pathology Resource

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10.1038/s41588-020-00748-0

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Conti, D. V., Darst, B. F., Moss, L. C., Saunders, E. J., Sheng, X., Chou, A., Schumacher, F. R., Olama, A. A. A., Benlloch, S., Dadaev, T., Brook, M. N., Sahimi, A., Hoffmann, T. J., Takahashi, A., Matsuda, K., Momozawa, Y., Fujita, M., Muir, K., Lophatananon, A., ... Haiman, C. A. (2021). Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction. Nature Genetics, 53(1), 65-75. https://doi.org/10.1038/s41588-020-00748-0

Conti, DV, Darst, BF, Moss, LC, Saunders, EJ, Sheng, X, Chou, A, Schumacher, FR, Olama, AAA, Benlloch, S, Dadaev, T, Brook, MN, Sahimi, A, Hoffmann, TJ, Takahashi, A, Matsuda, K, Momozawa, Y, Fujita, M, Muir, K, Lophatananon, A, Wan, P, Le Marchand, L, Wilkens, LR, Stevens, VL, Gapstur, SM, Carter, BD, Schleutker, J, Tammela, TLJ, Sipeky, C, Auvinen, A, Giles, GG, Southey, MC, MacInnis, RJ, Cybulski, C, Wokołorczyk, D, Lubiński, J, Neal, DE, Donovan, JL, Hamdy, FC, Martin, RM, Nordestgaard, BG, Nielsen, SF, Weischer, M, Bojesen, SE, Røder, MA, Iversen, P, Batra, J, Chambers, S, Moya, L, Horvath, L, Clements, JA, Tilley, W, Risbridger, GP, Gronberg, H, Aly, M, Szulkin, R, Eklund, M, Nordström, T, Pashayan, N, Dunning, AM, Ghoussaini, M, Travis, RC, Key, TJ, Riboli, E, Park, JY, Sellers, TA, Lin, HY, Albanes, D, Weinstein, SJ, 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, Geybels, MS, Koutros, S, Freeman, LEB, 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, Burnet, N, 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, Fontham, ETH, Mohler, J, Taylor, JA, Kogevinas, M, Llorca, J, Castaño-Vinyals, G, Cannon-Albright, L, Teerlink, CC, Huff, CD, Strom, SS, Multigner, L, Blanchet, P, Brureau, L, Kaneva, R, Slavov, C, Mitev, V, Leach, RJ, Weaver, B, Brenner, H, Cuk, K, Holleczek, B, Saum, KU, 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, C, Rybicki, BA, Gamulin, M, Lessel, D, Kulis, T, Usmani, N, 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, JC, Petrovics, G, Casey, G, Roobol, MJ, Jenster, G, van Schaik, RHN, Hu, JJ, Sanderson, M, Varma, R, McKean-Cowdin, R, Torres, M, Mancuso, N, Berndt, SI, Van Den Eeden, SK, Easton, DF, Chanock, SJ, Cook, MB, Wiklund, F, Nakagawa, H, Witte, JS, Eeles, RA, Kote-Jarai, Z & Haiman, CA 2021, 'Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction', Nature Genetics, vol. 53, no. 1, pp. 65-75. https://doi.org/10.1038/s41588-020-00748-0

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title = "Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction",

abstract = "Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84–5.29) for men of European ancestry to 3.74 (95% CI, 3.36–4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14–2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71–0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.",

author = "Conti, {David V.} and Darst, {Burcu F.} and Moss, {Lilit C.} and Saunders, {Edward J.} and Xin Sheng and Alisha Chou and Schumacher, {Fredrick R.} and Olama, {Ali Amin Al} and Sara Benlloch and Tokhir Dadaev and Brook, {Mark N.} and Ali Sahimi and Hoffmann, {Thomas J.} and Atushi Takahashi and Koichi Matsuda and Yukihide Momozawa and Masashi Fujita and Kenneth Muir and Artitaya Lophatananon and Peggy Wan and {Le Marchand}, Loic and Wilkens, {Lynne R.} and Stevens, {Victoria L.} and Gapstur, {Susan M.} and Carter, {Brian D.} 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 Woko{\l}orczyk and Jan Lubi{\'n}ski and Neal, {David E.} and Donovan, {Jenny L.} and Hamdy, {Freddie C.} and Martin, {Richard M.} and Nordestgaard, {B{\o}rge G.} and Nielsen, {Sune F.} and Maren Weischer and Bojesen, {Stig E.} and R{\o}der, {Martin Andreas} and Peter Iversen and Jyotsna Batra and Suzanne Chambers and Leire Moya and Lisa Horvath and Clements, {Judith A.} and Wayne Tilley and Risbridger, {Gail P.} and Henrik Gronberg and Markus Aly and Robert Szulkin and Martin Eklund and Tobias Nordstr{\"o}m 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 Weinstein, {Stephanie J.} 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 Geybels, {Milan S.} and Stella Koutros and Freeman, {Laura E.Beane} 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 Neil Burnet and Gill Barnett and Christiane Maier and Thomas Schnoeller and Manuel Luedeke and Kibel, {Adam S.} and Drake, {Bettina F.} and Olivier Cussenot and G{\'e}raldine 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 Fontham, {Elizabeth T.H.} and James Mohler and Taylor, {Jack A.} and Manolis Kogevinas and Javier Llorca and Gemma Casta{\~n}o-Vinyals and Lisa Cannon-Albright and Teerlink, {Craig C.} and Huff, {Chad D.} 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 Brandi Weaver and Hermann Brenner and Katarina Cuk and Bernd Holleczek and Saum, {Kai Uwe} and Klein, {Eric A.} and Hsing, {Ann W.} and Kittles, {Rick A.} and Murphy, {Adam B.} and Logothetis, {Christopher J.} and Jeri Kim and Neuhausen, {Susan L.} and Linda Steele and Ding, {Yuan Chun} and Isaacs, {William B.} and Barbara Nemesure and Hennis, {Anselm J.M.} and John Carpten and Hardev Pandha and Agnieszka Michael and {De Ruyck}, Kim and {De Meerleer}, Gert and Piet Ost and Jianfeng Xu and Azad Razack and Jasmine Lim and Teo, {Soo Hwang} and Newcomb, {Lisa F.} and Lin, {Daniel W.} and Fowke, {Jay H.} and Christine Neslund-Dudas and Rybicki, {Benjamin A.} and Marija Gamulin and Davor Lessel and Tomislav Kulis and Nawaid Usmani and Sandeep Singhal and Matthew Parliament and Frank Claessens and Steven Joniau and {Van den Broeck}, Thomas and Manuela Gago-Dominguez and Castelao, {Jose Esteban} and Martinez, {Maria Elena} and Samantha Larkin and Townsend, {Paul A.} and Claire Aukim-Hastie and Bush, {William S.} and Aldrich, {Melinda C.} and Crawford, {Dana C.} and Shiv Srivastava and Cullen, {Jennifer C.} and Gyorgy Petrovics and Graham Casey and Roobol, {Monique J.} and Guido Jenster and {van Schaik}, {Ron H.N.} and Hu, {Jennifer J.} and Maureen Sanderson and Rohit Varma and Roberta McKean-Cowdin and Mina Torres and Nicholas Mancuso and Berndt, {Sonja I.} and {Van Den Eeden}, {Stephen K.} and Easton, {Douglas F.} and Chanock, {Stephen J.} and Cook, {Michael B.} and Fredrik Wiklund and Hidewaki Nakagawa and Witte, {John S.} and Eeles, {Rosalind A.} and Zsofia Kote-Jarai and Haiman, {Christopher A.}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2021",

month = jan,

doi = "10.1038/s41588-020-00748-0",

language = "English (US)",

volume = "53",

pages = "65--75",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

AU - Conti, David V.

AU - Darst, Burcu F.

AU - Moss, Lilit C.

AU - Saunders, Edward J.

AU - Sheng, Xin

AU - Chou, Alisha

AU - Schumacher, Fredrick R.

AU - Olama, Ali Amin Al

AU - Benlloch, Sara

AU - Dadaev, Tokhir

AU - Brook, Mark N.

AU - Sahimi, Ali

AU - Hoffmann, Thomas J.

AU - Takahashi, Atushi

AU - Matsuda, Koichi

AU - Momozawa, Yukihide

AU - Fujita, Masashi

AU - Muir, Kenneth

AU - Lophatananon, Artitaya

AU - Wan, Peggy

AU - Le Marchand, Loic

AU - Wilkens, Lynne R.

AU - Stevens, Victoria L.

AU - Gapstur, Susan M.

AU - Carter, Brian D.

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 - Wokołorczyk, Dominika

AU - Lubiński, Jan

AU - Neal, David E.

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Martin, Richard M.

AU - Nordestgaard, Børge G.

AU - Nielsen, Sune F.

AU - Weischer, Maren

AU - Bojesen, Stig E.

AU - Røder, Martin Andreas

AU - Iversen, Peter

AU - Batra, Jyotsna

AU - Chambers, Suzanne

AU - Moya, Leire

AU - Horvath, Lisa

AU - Clements, Judith A.

AU - Tilley, Wayne

AU - Risbridger, Gail P.

AU - Gronberg, Henrik

AU - Aly, Markus

AU - Szulkin, Robert

AU - Eklund, Martin

AU - Nordström, 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 J.

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 - Geybels, Milan S.

AU - Koutros, Stella

AU - Freeman, Laura E.Beane

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 - Burnet, Neil

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, Géraldine

AU - Menegaux, Florence

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AU - Kote-Jarai, Zsofia

AU - Haiman, Christopher A.

PY - 2021/1

Y1 - 2021/1

N2 - Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84–5.29) for men of European ancestry to 3.74 (95% CI, 3.36–4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14–2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71–0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

AB - Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84–5.29) for men of European ancestry to 3.74 (95% CI, 3.36–4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14–2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71–0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

UR - http://www.scopus.com/inward/record.url?scp=85098923871&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85098923871&partnerID=8YFLogxK

U2 - 10.1038/s41588-020-00748-0

DO - 10.1038/s41588-020-00748-0

M3 - Article

C2 - 33398198

AN - SCOPUS:85098923871

SN - 1061-4036

VL - 53

SP - 65

EP - 75

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

Abstract

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MD Anderson CCSG core facilities

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