Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

Fredrick R. Schumacher, Ali Amin Al Olama, Sonja I. Berndt, Sara Benlloch, Mahbubl Ahmed, Edward J. Saunders, Tokhir Dadaev, Daniel Leongamornlert, Ezequiel Anokian, Clara Cieza-Borrella, Chee Goh, Mark N. Brook, Xin Sheng, Laura Fachal, Joe Dennis, Jonathan Tyrer, Kenneth Muir, Artitaya Lophatananon, Victoria L. Stevens, Susan M. Gapstur & 167 others Brian D. Carter, Catherine M. Tangen, Phyllis J. Goodman, Ian M. Thompson, Jyotsna Batra, Suzanne Chambers, Leire Moya, Judith Clements, Lisa Horvath, Wayne Tilley, Gail P. Risbridger, Henrik Gronberg, Markus Aly, Tobias Nordström, Paul Pharoah, Nora Pashayan, Johanna Schleutker, Teuvo L.J. Tammela, Csilla Sipeky, Anssi Auvinen, Demetrius Albanes, Stephanie Weinstein, Alicja Wolk, Niclas Håkansson, Catharine M.L. West, Alison M. Dunning, Neil Burnet, Lorelei A. Mucci, Edward Giovannucci, Gerald L. Andriole, Olivier Cussenot, Géraldine Cancel-Tassin, Stella Koutros, Laura E. Beane Freeman, Karina Dalsgaard Sorensen, Torben Falck Orntoft, Michael Borre, Lovise Maehle, Eli Marie Grindedal, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Ruth C. Travis, Tim J. Key, Robert J. Hamilton, Neil E. Fleshner, Antonio Finelli, Sue Ann Ingles, Mariana C. Stern, Barry S. Rosenstein, Sarah L. Kerns, Harry Ostrer, Yong Jie Lu, Hong Wei Zhang, Ninghan Feng, Xueying Mao, Xin Guo, Guomin Wang, Zan Sun, Graham G. Giles, Melissa C. Southey, Robert J. MacInnis, Liesel M. Fitzgerald, Adam S. Kibel, Bettina F. Drake, Ana Vega, Antonio Gómez-Caamaño, Robert Szulkin, Martin Eklund, Manolis Kogevinas, Javier Llorca, Gemma Castaño-Vinyals, Kathryn L. Penney, Meir Stampfer, Jong Y. Park, Thomas A. Sellers, Hui Yi Lin, Janet L. Stanford, Cezary Cybulski, Dominika Wokolorczyk, Jan Lubinski, Elaine A. Ostrander, Milan S. Geybels, Børge G. Nordestgaard, Sune F. Nielsen, Maren Weischer, Rasmus Bisbjerg, Martin Andreas Røder, Peter Iversen, Hermann Brenner, Katarina Cuk, Bernd Holleczek, Christiane Maier, Manuel Luedeke, Thomas Schnoeller, Jeri Kim, Christopher J. Logothetis, Esther M. John, Manuel R. Teixeira, Paula Paulo, Marta Cardoso, Susan L. Neuhausen, Linda Steele, Yuan Chun Ding, Kim De Ruyck, Gert De Meerleer, Piet Ost, Azad Razack, Jasmine Lim, Soo Hwang Teo, Daniel W. Lin, Lisa F. Newcomb, Davor Lessel, Marija Gamulin, Tomislav Kulis, Radka Kaneva, Nawaid Usmani, Sandeep Singhal, Chavdar Slavov, Vanio Mitev, Matthew Parliament, Frank Claessens, Steven Joniau, Thomas Van Den Broeck, Samantha Larkin, Paul A. Townsend, Claire Aukim-Hastie, Manuela Gago Dominguez, Jose Esteban Castelao, Maria Elena Martinez, Monique J. Roobol, Guido Jenster, Ron H.N. Van Schaik, Florence Menegaux, Thérèse Truong, Yves Akoli Koudou, Jianfeng Xu, Kay Tee Khaw, Lisa Cannon-Albright, Hardev Pandha, Agnieszka Michael, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Sara Lindstrom, Constance Turman, Jing Ma, David J. Hunter, Elio Riboli, Afshan Siddiq, Federico Canzian, Laurence N. Kolonel, Loic Le Marchand, Robert N. Hoover, Mitchell J. Machiela, Zuxi Cui, Peter Kraft, Christopher I. Amos, David V. Conti, Douglas F. Easton, Fredrik Wiklund, Stephen J. Chanock, Brian E. Henderson, Zsofia Kote-Jarai, Christopher A. Haiman, Rosalind A. Eeles

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa 1 .

Original languageEnglish
Pages (from-to)928-936
Number of pages9
JournalNature Genetics
Volume50
Issue number7
DOIs
Publication statusPublished - 1 Jul 2018

Cite this

Schumacher, F. R., Al Olama, A. A., Berndt, S. I., Benlloch, S., Ahmed, M., Saunders, E. J., ... Eeles, R. A. (2018). Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci. Nature Genetics, 50(7), 928-936. https://doi.org/10.1038/s41588-018-0142-8
Schumacher, Fredrick R. ; Al Olama, Ali Amin ; Berndt, Sonja I. ; Benlloch, Sara ; Ahmed, Mahbubl ; Saunders, Edward J. ; Dadaev, Tokhir ; Leongamornlert, Daniel ; Anokian, Ezequiel ; Cieza-Borrella, Clara ; Goh, Chee ; Brook, Mark N. ; Sheng, Xin ; Fachal, Laura ; Dennis, Joe ; Tyrer, Jonathan ; Muir, Kenneth ; Lophatananon, Artitaya ; Stevens, Victoria L. ; Gapstur, Susan M. ; Carter, Brian D. ; Tangen, Catherine M. ; Goodman, Phyllis J. ; Thompson, Ian M. ; Batra, Jyotsna ; Chambers, Suzanne ; Moya, Leire ; Clements, Judith ; Horvath, Lisa ; Tilley, Wayne ; Risbridger, Gail P. ; Gronberg, Henrik ; Aly, Markus ; Nordström, Tobias ; Pharoah, Paul ; Pashayan, Nora ; Schleutker, Johanna ; Tammela, Teuvo L.J. ; Sipeky, Csilla ; Auvinen, Anssi ; Albanes, Demetrius ; Weinstein, Stephanie ; Wolk, Alicja ; Håkansson, Niclas ; West, Catharine M.L. ; Dunning, Alison M. ; Burnet, Neil ; Mucci, Lorelei A. ; Giovannucci, Edward ; Andriole, Gerald L. ; Cussenot, Olivier ; Cancel-Tassin, Géraldine ; Koutros, Stella ; Beane Freeman, Laura E. ; Sorensen, Karina Dalsgaard ; Orntoft, Torben Falck ; Borre, Michael ; Maehle, Lovise ; Grindedal, Eli Marie ; Neal, David E. ; Donovan, Jenny L. ; Hamdy, Freddie C. ; Martin, Richard M. ; Travis, Ruth C. ; Key, Tim J. ; Hamilton, Robert J. ; Fleshner, Neil E. ; Finelli, Antonio ; Ingles, Sue Ann ; Stern, Mariana C. ; Rosenstein, Barry S. ; Kerns, Sarah L. ; Ostrer, Harry ; Lu, Yong Jie ; Zhang, Hong Wei ; Feng, Ninghan ; Mao, Xueying ; Guo, Xin ; Wang, Guomin ; Sun, Zan ; Giles, Graham G. ; Southey, Melissa C. ; MacInnis, Robert J. ; Fitzgerald, Liesel M. ; Kibel, Adam S. ; Drake, Bettina F. ; Vega, Ana ; Gómez-Caamaño, Antonio ; Szulkin, Robert ; Eklund, Martin ; Kogevinas, Manolis ; Llorca, Javier ; Castaño-Vinyals, Gemma ; Penney, Kathryn L. ; Stampfer, Meir ; Park, Jong Y. ; Sellers, Thomas A. ; Lin, Hui Yi ; Stanford, Janet L. ; Cybulski, Cezary ; Wokolorczyk, Dominika ; Lubinski, Jan ; Ostrander, Elaine A. ; Geybels, Milan S. ; Nordestgaard, Børge G. ; Nielsen, Sune F. ; Weischer, Maren ; Bisbjerg, Rasmus ; Røder, Martin Andreas ; Iversen, Peter ; Brenner, Hermann ; Cuk, Katarina ; Holleczek, Bernd ; Maier, Christiane ; Luedeke, Manuel ; Schnoeller, Thomas ; Kim, Jeri ; Logothetis, Christopher J. ; John, Esther M. ; Teixeira, Manuel R. ; Paulo, Paula ; Cardoso, Marta ; Neuhausen, Susan L. ; Steele, Linda ; Ding, Yuan Chun ; De Ruyck, Kim ; De Meerleer, Gert ; Ost, Piet ; Razack, Azad ; Lim, Jasmine ; Teo, Soo Hwang ; Lin, Daniel W. ; Newcomb, Lisa F. ; Lessel, Davor ; Gamulin, Marija ; Kulis, Tomislav ; Kaneva, Radka ; Usmani, Nawaid ; Singhal, Sandeep ; Slavov, Chavdar ; Mitev, Vanio ; Parliament, Matthew ; Claessens, Frank ; Joniau, Steven ; Van Den Broeck, Thomas ; Larkin, Samantha ; Townsend, Paul A. ; Aukim-Hastie, Claire ; Dominguez, Manuela Gago ; Castelao, Jose Esteban ; Martinez, Maria Elena ; Roobol, Monique J. ; Jenster, Guido ; Van Schaik, Ron H.N. ; Menegaux, Florence ; Truong, Thérèse ; Koudou, Yves Akoli ; Xu, Jianfeng ; Khaw, Kay Tee ; Cannon-Albright, Lisa ; Pandha, Hardev ; Michael, Agnieszka ; Thibodeau, Stephen N. ; McDonnell, Shannon K. ; Schaid, Daniel J. ; Lindstrom, Sara ; Turman, Constance ; Ma, Jing ; Hunter, David J. ; Riboli, Elio ; Siddiq, Afshan ; Canzian, Federico ; Kolonel, Laurence N. ; Le Marchand, Loic ; Hoover, Robert N. ; Machiela, Mitchell J. ; Cui, Zuxi ; Kraft, Peter ; Amos, Christopher I. ; Conti, David V. ; Easton, Douglas F. ; Wiklund, Fredrik ; Chanock, Stephen J. ; Henderson, Brian E. ; Kote-Jarai, Zsofia ; Haiman, Christopher A. ; Eeles, Rosalind A. / Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci. In: Nature Genetics. 2018 ; Vol. 50, No. 7. pp. 928-936.
@article{7abb90d7208b4232975713a183232ea2,
title = "Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci",
abstract = "Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4{\%} of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95{\%} confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95{\%} CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa 1 .",
author = "Schumacher, {Fredrick R.} and {Al Olama}, {Ali Amin} and Berndt, {Sonja I.} and Sara Benlloch and Mahbubl Ahmed and Saunders, {Edward J.} and Tokhir Dadaev and Daniel Leongamornlert and Ezequiel Anokian and Clara Cieza-Borrella and Chee Goh and Brook, {Mark N.} and Xin Sheng and Laura Fachal and Joe Dennis and Jonathan Tyrer and Kenneth Muir and Artitaya Lophatananon and Stevens, {Victoria L.} and Gapstur, {Susan M.} and Carter, {Brian D.} and Tangen, {Catherine M.} and Goodman, {Phyllis J.} and Thompson, {Ian M.} and Jyotsna Batra and Suzanne Chambers and Leire Moya and Judith Clements and Lisa Horvath and Wayne Tilley and Risbridger, {Gail P.} and Henrik Gronberg and Markus Aly and Tobias Nordstr{\"o}m and Paul Pharoah and Nora Pashayan and Johanna Schleutker and Tammela, {Teuvo L.J.} and Csilla Sipeky and Anssi Auvinen and Demetrius Albanes and Stephanie Weinstein and Alicja Wolk and Niclas H{\aa}kansson and West, {Catharine M.L.} and Dunning, {Alison M.} and Neil Burnet and Mucci, {Lorelei A.} and Edward Giovannucci and Andriole, {Gerald L.} and Olivier Cussenot and G{\'e}raldine Cancel-Tassin and Stella Koutros and {Beane Freeman}, {Laura E.} and Sorensen, {Karina Dalsgaard} and Orntoft, {Torben Falck} and Michael Borre and Lovise Maehle and Grindedal, {Eli Marie} and Neal, {David E.} and Donovan, {Jenny L.} and Hamdy, {Freddie C.} and Martin, {Richard M.} and Travis, {Ruth C.} and Key, {Tim J.} and Hamilton, {Robert J.} and Fleshner, {Neil E.} and Antonio Finelli and Ingles, {Sue Ann} and Stern, {Mariana C.} and Rosenstein, {Barry S.} and Kerns, {Sarah L.} and Harry Ostrer and Lu, {Yong Jie} and Zhang, {Hong Wei} and Ninghan Feng and Xueying Mao and Xin Guo and Guomin Wang and Zan Sun and Giles, {Graham G.} and Southey, {Melissa C.} and MacInnis, {Robert J.} and Fitzgerald, {Liesel M.} and Kibel, {Adam S.} and Drake, {Bettina F.} and Ana Vega and Antonio G{\'o}mez-Caama{\~n}o and Robert Szulkin and Martin Eklund and Manolis Kogevinas and Javier Llorca and Gemma Casta{\~n}o-Vinyals and Penney, {Kathryn L.} and Meir Stampfer and Park, {Jong Y.} and Sellers, {Thomas A.} and Lin, {Hui Yi} and Stanford, {Janet L.} and Cezary Cybulski and Dominika Wokolorczyk and Jan Lubinski and Ostrander, {Elaine A.} and Geybels, {Milan S.} and Nordestgaard, {B{\o}rge G.} and Nielsen, {Sune F.} and Maren Weischer and Rasmus Bisbjerg and R{\o}der, {Martin Andreas} and Peter Iversen and Hermann Brenner and Katarina Cuk and Bernd Holleczek and Christiane Maier and Manuel Luedeke and Thomas Schnoeller and Jeri Kim and Logothetis, {Christopher J.} and John, {Esther M.} and Teixeira, {Manuel R.} and Paula Paulo and Marta Cardoso and Neuhausen, {Susan L.} and Linda Steele and Ding, {Yuan Chun} and {De Ruyck}, Kim and {De Meerleer}, Gert and Piet Ost and Azad Razack and Jasmine Lim and Teo, {Soo Hwang} and Lin, {Daniel W.} and Newcomb, {Lisa F.} and Davor Lessel and Marija Gamulin and Tomislav Kulis and Radka Kaneva and Nawaid Usmani and Sandeep Singhal and Chavdar Slavov and Vanio Mitev and Matthew Parliament and Frank Claessens and Steven Joniau and {Van Den Broeck}, Thomas and Samantha Larkin and Townsend, {Paul A.} and Claire Aukim-Hastie and Dominguez, {Manuela Gago} and Castelao, {Jose Esteban} and Martinez, {Maria Elena} and Roobol, {Monique J.} and Guido Jenster and {Van Schaik}, {Ron H.N.} and Florence Menegaux and Th{\'e}r{\`e}se Truong and Koudou, {Yves Akoli} and Jianfeng Xu and Khaw, {Kay Tee} and Lisa Cannon-Albright and Hardev Pandha and Agnieszka Michael and Thibodeau, {Stephen N.} and McDonnell, {Shannon K.} and Schaid, {Daniel J.} and Sara Lindstrom and Constance Turman and Jing Ma and Hunter, {David J.} and Elio Riboli and Afshan Siddiq and Federico Canzian and Kolonel, {Laurence N.} and {Le Marchand}, Loic and Hoover, {Robert N.} and Machiela, {Mitchell J.} and Zuxi Cui and Peter Kraft and Amos, {Christopher I.} and Conti, {David V.} and Easton, {Douglas F.} and Fredrik Wiklund and Chanock, {Stephen J.} and Henderson, {Brian E.} and Zsofia Kote-Jarai and Haiman, {Christopher A.} and Eeles, {Rosalind A.}",
year = "2018",
month = "7",
day = "1",
doi = "10.1038/s41588-018-0142-8",
language = "English",
volume = "50",
pages = "928--936",
journal = "Nature Genetics",
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Schumacher, FR, Al Olama, AA, Berndt, SI, Benlloch, S, Ahmed, M, Saunders, EJ, Dadaev, T, Leongamornlert, D, Anokian, E, Cieza-Borrella, C, Goh, C, Brook, MN, Sheng, X, Fachal, L, Dennis, J, Tyrer, J, Muir, K, Lophatananon, A, Stevens, VL, Gapstur, SM, Carter, BD, Tangen, CM, Goodman, PJ, Thompson, IM, Batra, J, Chambers, S, Moya, L, Clements, J, Horvath, L, Tilley, W, Risbridger, GP, Gronberg, H, Aly, M, Nordström, T, Pharoah, P, Pashayan, N, Schleutker, J, Tammela, TLJ, Sipeky, C, Auvinen, A, Albanes, D, Weinstein, S, Wolk, A, Håkansson, N, West, CML, Dunning, AM, Burnet, N, Mucci, LA, Giovannucci, E, Andriole, GL, Cussenot, O, Cancel-Tassin, G, Koutros, S, Beane Freeman, LE, Sorensen, KD, Orntoft, TF, Borre, M, Maehle, L, Grindedal, EM, Neal, DE, Donovan, JL, Hamdy, FC, Martin, RM, Travis, RC, Key, TJ, Hamilton, RJ, Fleshner, NE, Finelli, A, Ingles, SA, Stern, MC, Rosenstein, BS, Kerns, SL, Ostrer, H, Lu, YJ, Zhang, HW, Feng, N, Mao, X, Guo, X, Wang, G, Sun, Z, Giles, GG, Southey, MC, MacInnis, RJ, Fitzgerald, LM, Kibel, AS, Drake, BF, Vega, A, Gómez-Caamaño, A, Szulkin, R, Eklund, M, Kogevinas, M, Llorca, J, Castaño-Vinyals, G, Penney, KL, Stampfer, M, Park, JY, Sellers, TA, Lin, HY, Stanford, JL, Cybulski, C, Wokolorczyk, D, Lubinski, J, Ostrander, EA, Geybels, MS, Nordestgaard, BG, Nielsen, SF, Weischer, M, Bisbjerg, R, Røder, MA, Iversen, P, Brenner, H, Cuk, K, Holleczek, B, Maier, C, Luedeke, M, Schnoeller, T, Kim, J, Logothetis, CJ, John, EM, Teixeira, MR, Paulo, P, Cardoso, M, Neuhausen, SL, Steele, L, Ding, YC, De Ruyck, K, De Meerleer, G, Ost, P, Razack, A, Lim, J, Teo, SH, Lin, DW, Newcomb, LF, Lessel, D, Gamulin, M, Kulis, T, Kaneva, R, Usmani, N, Singhal, S, Slavov, C, Mitev, V, Parliament, M, Claessens, F, Joniau, S, Van Den Broeck, T, Larkin, S, Townsend, PA, Aukim-Hastie, C, Dominguez, MG, Castelao, JE, Martinez, ME, Roobol, MJ, Jenster, G, Van Schaik, RHN, Menegaux, F, Truong, T, Koudou, YA, Xu, J, Khaw, KT, Cannon-Albright, L, Pandha, H, Michael, A, Thibodeau, SN, McDonnell, SK, Schaid, DJ, Lindstrom, S, Turman, C, Ma, J, Hunter, DJ, Riboli, E, Siddiq, A, Canzian, F, Kolonel, LN, Le Marchand, L, Hoover, RN, Machiela, MJ, Cui, Z, Kraft, P, Amos, CI, Conti, DV, Easton, DF, Wiklund, F, Chanock, SJ, Henderson, BE, Kote-Jarai, Z, Haiman, CA & Eeles, RA 2018, 'Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci' Nature Genetics, vol. 50, no. 7, pp. 928-936. https://doi.org/10.1038/s41588-018-0142-8

Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci. / Schumacher, Fredrick R.; Al Olama, Ali Amin; Berndt, Sonja I.; Benlloch, Sara; Ahmed, Mahbubl; Saunders, Edward J.; Dadaev, Tokhir; Leongamornlert, Daniel; Anokian, Ezequiel; Cieza-Borrella, Clara; Goh, Chee; Brook, Mark N.; Sheng, Xin; Fachal, Laura; Dennis, Joe; Tyrer, Jonathan; Muir, Kenneth; Lophatananon, Artitaya; Stevens, Victoria L.; Gapstur, Susan M.; Carter, Brian D.; Tangen, Catherine M.; Goodman, Phyllis J.; Thompson, Ian M.; Batra, Jyotsna; Chambers, Suzanne; Moya, Leire; Clements, Judith; Horvath, Lisa; Tilley, Wayne; Risbridger, Gail P.; Gronberg, Henrik; Aly, Markus; Nordström, Tobias; Pharoah, Paul; Pashayan, Nora; Schleutker, Johanna; Tammela, Teuvo L.J.; Sipeky, Csilla; Auvinen, Anssi; Albanes, Demetrius; Weinstein, Stephanie; Wolk, Alicja; Håkansson, Niclas; West, Catharine M.L.; Dunning, Alison M.; Burnet, Neil; Mucci, Lorelei A.; Giovannucci, Edward; Andriole, Gerald L.; Cussenot, Olivier; Cancel-Tassin, Géraldine; Koutros, Stella; Beane Freeman, Laura E.; Sorensen, Karina Dalsgaard; Orntoft, Torben Falck; Borre, Michael; Maehle, Lovise; Grindedal, Eli Marie; Neal, David E.; Donovan, Jenny L.; Hamdy, Freddie C.; Martin, Richard M.; Travis, Ruth C.; Key, Tim J.; Hamilton, Robert J.; Fleshner, Neil E.; Finelli, Antonio; Ingles, Sue Ann; Stern, Mariana C.; Rosenstein, Barry S.; Kerns, Sarah L.; Ostrer, Harry; Lu, Yong Jie; Zhang, Hong Wei; Feng, Ninghan; Mao, Xueying; Guo, Xin; Wang, Guomin; Sun, Zan; Giles, Graham G.; Southey, Melissa C.; MacInnis, Robert J.; Fitzgerald, Liesel M.; Kibel, Adam S.; Drake, Bettina F.; Vega, Ana; Gómez-Caamaño, Antonio; Szulkin, Robert; Eklund, Martin; Kogevinas, Manolis; Llorca, Javier; Castaño-Vinyals, Gemma; Penney, Kathryn L.; Stampfer, Meir; Park, Jong Y.; Sellers, Thomas A.; Lin, Hui Yi; Stanford, Janet L.; Cybulski, Cezary; Wokolorczyk, Dominika; Lubinski, Jan; Ostrander, Elaine A.; Geybels, Milan S.; Nordestgaard, Børge G.; Nielsen, Sune F.; Weischer, Maren; Bisbjerg, Rasmus; Røder, Martin Andreas; Iversen, Peter; Brenner, Hermann; Cuk, Katarina; Holleczek, Bernd; Maier, Christiane; Luedeke, Manuel; Schnoeller, Thomas; Kim, Jeri; Logothetis, Christopher J.; John, Esther M.; Teixeira, Manuel R.; Paulo, Paula; Cardoso, Marta; Neuhausen, Susan L.; Steele, Linda; Ding, Yuan Chun; De Ruyck, Kim; De Meerleer, Gert; Ost, Piet; Razack, Azad; Lim, Jasmine; Teo, Soo Hwang; Lin, Daniel W.; Newcomb, Lisa F.; Lessel, Davor; Gamulin, Marija; Kulis, Tomislav; Kaneva, Radka; Usmani, Nawaid; Singhal, Sandeep; Slavov, Chavdar; Mitev, Vanio; Parliament, Matthew; Claessens, Frank; Joniau, Steven; Van Den Broeck, Thomas; Larkin, Samantha; Townsend, Paul A.; Aukim-Hastie, Claire; Dominguez, Manuela Gago; Castelao, Jose Esteban; Martinez, Maria Elena; Roobol, Monique J.; Jenster, Guido; Van Schaik, Ron H.N.; Menegaux, Florence; Truong, Thérèse; Koudou, Yves Akoli; Xu, Jianfeng; Khaw, Kay Tee; Cannon-Albright, Lisa; Pandha, Hardev; Michael, Agnieszka; Thibodeau, Stephen N.; McDonnell, Shannon K.; Schaid, Daniel J.; Lindstrom, Sara; Turman, Constance; Ma, Jing; Hunter, David J.; Riboli, Elio; Siddiq, Afshan; Canzian, Federico; Kolonel, Laurence N.; Le Marchand, Loic; Hoover, Robert N.; Machiela, Mitchell J.; Cui, Zuxi; Kraft, Peter; Amos, Christopher I.; Conti, David V.; Easton, Douglas F.; Wiklund, Fredrik; Chanock, Stephen J.; Henderson, Brian E.; Kote-Jarai, Zsofia; Haiman, Christopher A.; Eeles, Rosalind A.

In: Nature Genetics, Vol. 50, No. 7, 01.07.2018, p. 928-936.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci

AU - Schumacher, Fredrick R.

AU - Al Olama, Ali Amin

AU - Berndt, Sonja I.

AU - Benlloch, Sara

AU - Ahmed, Mahbubl

AU - Saunders, Edward J.

AU - Dadaev, Tokhir

AU - Leongamornlert, Daniel

AU - Anokian, Ezequiel

AU - Cieza-Borrella, Clara

AU - Goh, Chee

AU - Brook, Mark N.

AU - Sheng, Xin

AU - Fachal, Laura

AU - Dennis, Joe

AU - Tyrer, Jonathan

AU - Muir, Kenneth

AU - Lophatananon, Artitaya

AU - Stevens, Victoria L.

AU - Gapstur, Susan M.

AU - Carter, Brian D.

AU - Tangen, Catherine M.

AU - Goodman, Phyllis J.

AU - Thompson, Ian M.

AU - Batra, Jyotsna

AU - Chambers, Suzanne

AU - Moya, Leire

AU - Clements, Judith

AU - Horvath, Lisa

AU - Tilley, Wayne

AU - Risbridger, Gail P.

AU - Gronberg, Henrik

AU - Aly, Markus

AU - Nordström, Tobias

AU - Pharoah, Paul

AU - Pashayan, Nora

AU - Schleutker, Johanna

AU - Tammela, Teuvo L.J.

AU - Sipeky, Csilla

AU - Auvinen, Anssi

AU - Albanes, Demetrius

AU - Weinstein, Stephanie

AU - Wolk, Alicja

AU - Håkansson, Niclas

AU - West, Catharine M.L.

AU - Dunning, Alison M.

AU - Burnet, Neil

AU - Mucci, Lorelei A.

AU - Giovannucci, Edward

AU - Andriole, Gerald L.

AU - Cussenot, Olivier

AU - Cancel-Tassin, Géraldine

AU - Koutros, Stella

AU - Beane Freeman, Laura E.

AU - Sorensen, Karina Dalsgaard

AU - Orntoft, Torben Falck

AU - Borre, Michael

AU - Maehle, Lovise

AU - Grindedal, Eli Marie

AU - Neal, David E.

AU - Donovan, Jenny L.

AU - Hamdy, Freddie C.

AU - Martin, Richard M.

AU - Travis, Ruth C.

AU - Key, Tim J.

AU - Hamilton, Robert J.

AU - Fleshner, Neil E.

AU - Finelli, Antonio

AU - Ingles, Sue Ann

AU - Stern, Mariana C.

AU - Rosenstein, Barry S.

AU - Kerns, Sarah L.

AU - Ostrer, Harry

AU - Lu, Yong Jie

AU - Zhang, Hong Wei

AU - Feng, Ninghan

AU - Mao, Xueying

AU - Guo, Xin

AU - Wang, Guomin

AU - Sun, Zan

AU - Giles, Graham G.

AU - Southey, Melissa C.

AU - MacInnis, Robert J.

AU - Fitzgerald, Liesel M.

AU - Kibel, Adam S.

AU - Drake, Bettina F.

AU - Vega, Ana

AU - Gómez-Caamaño, Antonio

AU - Szulkin, Robert

AU - Eklund, Martin

AU - Kogevinas, Manolis

AU - Llorca, Javier

AU - Castaño-Vinyals, Gemma

AU - Penney, Kathryn L.

AU - Stampfer, Meir

AU - Park, Jong Y.

AU - Sellers, Thomas A.

AU - Lin, Hui Yi

AU - Stanford, Janet L.

AU - Cybulski, Cezary

AU - Wokolorczyk, Dominika

AU - Lubinski, Jan

AU - Ostrander, Elaine A.

AU - Geybels, Milan S.

AU - Nordestgaard, Børge G.

AU - Nielsen, Sune F.

AU - Weischer, Maren

AU - Bisbjerg, Rasmus

AU - Røder, Martin Andreas

AU - Iversen, Peter

AU - Brenner, Hermann

AU - Cuk, Katarina

AU - Holleczek, Bernd

AU - Maier, Christiane

AU - Luedeke, Manuel

AU - Schnoeller, Thomas

AU - Kim, Jeri

AU - Logothetis, Christopher J.

AU - John, Esther M.

AU - Teixeira, Manuel R.

AU - Paulo, Paula

AU - Cardoso, Marta

AU - Neuhausen, Susan L.

AU - Steele, Linda

AU - Ding, Yuan Chun

AU - De Ruyck, Kim

AU - De Meerleer, Gert

AU - Ost, Piet

AU - Razack, Azad

AU - Lim, Jasmine

AU - Teo, Soo Hwang

AU - Lin, Daniel W.

AU - Newcomb, Lisa F.

AU - Lessel, Davor

AU - Gamulin, Marija

AU - Kulis, Tomislav

AU - Kaneva, Radka

AU - Usmani, Nawaid

AU - Singhal, Sandeep

AU - Slavov, Chavdar

AU - Mitev, Vanio

AU - Parliament, Matthew

AU - Claessens, Frank

AU - Joniau, Steven

AU - Van Den Broeck, Thomas

AU - Larkin, Samantha

AU - Townsend, Paul A.

AU - Aukim-Hastie, Claire

AU - Dominguez, Manuela Gago

AU - Castelao, Jose Esteban

AU - Martinez, Maria Elena

AU - Roobol, Monique J.

AU - Jenster, Guido

AU - Van Schaik, Ron H.N.

AU - Menegaux, Florence

AU - Truong, Thérèse

AU - Koudou, Yves Akoli

AU - Xu, Jianfeng

AU - Khaw, Kay Tee

AU - Cannon-Albright, Lisa

AU - Pandha, Hardev

AU - Michael, Agnieszka

AU - Thibodeau, Stephen N.

AU - McDonnell, Shannon K.

AU - Schaid, Daniel J.

AU - Lindstrom, Sara

AU - Turman, Constance

AU - Ma, Jing

AU - Hunter, David J.

AU - Riboli, Elio

AU - Siddiq, Afshan

AU - Canzian, Federico

AU - Kolonel, Laurence N.

AU - Le Marchand, Loic

AU - Hoover, Robert N.

AU - Machiela, Mitchell J.

AU - Cui, Zuxi

AU - Kraft, Peter

AU - Amos, Christopher I.

AU - Conti, David V.

AU - Easton, Douglas F.

AU - Wiklund, Fredrik

AU - Chanock, Stephen J.

AU - Henderson, Brian E.

AU - Kote-Jarai, Zsofia

AU - Haiman, Christopher A.

AU - Eeles, Rosalind A.

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa 1 .

AB - Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa 1 .

UR - http://www.scopus.com/inward/record.url?scp=85048333838&partnerID=8YFLogxK

U2 - 10.1038/s41588-018-0142-8

DO - 10.1038/s41588-018-0142-8

M3 - Article

VL - 50

SP - 928

EP - 936

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 7

ER -

Schumacher FR, Al Olama AA, Berndt SI, Benlloch S, Ahmed M, Saunders EJ et al. Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci. Nature Genetics. 2018 Jul 1;50(7):928-936. https://doi.org/10.1038/s41588-018-0142-8