Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
Authors
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.
Wan, P.
Le Marchand, L.
Wilkens, L. R.
Stevens, V. L.
Gapstur, S. M.
Carter, B. D.
Schleutker, J.
Tammela, T. L. J.
Sipeky, C.
Auvinen, A.
Giles, G. G.
Southey, M. C.
MacInnis, R. J.
Cybulski, C.
Wokołorczyk, D.
Lubiński, J.
Neal, D. E.
Donovan, J. L.
Hamdy, F. C.
Martin, R. M.
Nordestgaard, B. G.
Nielsen, S. F.
Weischer, M.
Bojesen, S. E.
Røder, M. A.
Iversen, P.
Batra, J.
Chambers, S.
Moya, L.
Horvath, L.
Clements, J. A.
Tilley, W.
Risbridger, G. P.
Gronberg, H.
Aly, M.
Szulkin, R.
Eklund, M.
Nordström, T.
Pashayan, N.
Dunning, A. M.
Ghoussaini, M.
Travis, R. C.
Key, T. J.
Riboli, E.
Park, J. Y.
Sellers, T. A.
Lin, H. Y.
Albanes, D.
Weinstein, S. J.
Mucci, L. A.
Giovannucci, E.
Lindstrom, S.
Kraft, P.
Hunter, D. J.
Penney, K. L.
Turman, C.
Tangen, C. M.
Goodman, P. J.
Thompson, I. M., Jr.
Hamilton, R. J.
Fleshner, N. E.
Finelli, A.
Parent, M.
Stanford, J. L.
Ostrander, E. A.
Geybels, M. S.
Koutros, S.
Freeman, L. E. B.
Stampfer, M.
Wolk, A.
Håkansson, N.
Andriole, G. L.
Hoover, R. N.
Machiela, M. J.
Sørensen, K. D.
Borre, M.
Blot, W. J.
Zheng, W.
Yeboah, E. D.
Mensah, J. E.
Lu, Y. J.
Zhang, H. W.
Feng, N.
Mao, X.
Wu, Y.
Zhao, S. C.
Sun, Z.
Thibodeau, S. N.
McDonnell, S. K.
Schaid, D. J.
West, Catharine M L
Burnet, Neil G
Barnett, G.
Maier, C.
Schnoeller, T.
Luedeke, M.
Kibel, A. S.
Drake, B. F.
Cussenot, O.
Cancel-Tassin, G.
Menegaux, F.
Truong, T.
Koudou, Y. A.
John, E. M.
Grindedal, E. M.
Maehle, L.
Khaw, K. T.
Ingles, S. A.
Stern, M. C.
Vega, A.
Gómez-Caamaño, A.
Fachal, L.
Rosenstein, B. S.
Kerns, S. L.
Ostrer, H.
Teixeira, M. R.
Paulo, P.
Brandão, A.
Watya, S.
Lubwama, A.
Bensen, J. T.
Fontham, E. T. H.
Mohler, J.
Taylor, J. A.
Kogevinas, M.
Llorca, J.
Castaño-Vinyals, G.
Cannon-Albright, L.
Teerlink, C. C.
Huff, C. D.
Strom, S. S.
Multigner, L.
Blanchet, P.
Brureau, L.
Kaneva, R.
Slavov, C.
Mitev, V.
Leach, R. J.
Weaver, B.
Brenner, H.
Cuk, K.
Holleczek, B.
Saum, K. U.
Klein, E. A.
Hsing, A. W.
Kittles, R. A.
Murphy, A. B.
Logothetis, C. J.
Kim, J.
Neuhausen, S. L.
Steele, L.
Ding, Y. C.
Isaacs, W. B.
Nemesure, B.
Hennis, A. J. M.
Carpten, J.
Pandha, H.
Michael, A.
De Ruyck, K.
De Meerleer, G.
Ost, P.
Xu, J.
Razack, A.
Lim, J.
Teo, S. H.
Newcomb, L. F.
Lin, D. W.
Fowke, J. H.
Neslund-Dudas, C.
Rybicki, B. A.
Gamulin, M.
Lessel, D.
Kulis, T.
Usmani, N.
Singhal, S.
Parliament, M.
Claessens, F.
Joniau, S.
Van den Broeck, T.
Gago-Dominguez, M.
Castelao, J. E.
Martinez, M. E.
Larkin, S.
Townsend, Paul A
Aukim-Hastie, C.
Bush, W. S.
Aldrich, M. C.
Crawford, D. C.
Srivastava, S.
Cullen, J. C.
Petrovics, G.
Casey, G.
Roobol, M. J.
Jenster, G.
van Schaik, R. H. N.
Hu, J. J.
Sanderson, M.
Varma, R.
McKean-Cowdin, R.
Torres, M.
Mancuso, N.
Berndt, S. I.
Van Den Eeden, S. K.
Easton, D. F.
Chanock, S. J.
Cook, M. B.
Wiklund, F.
Nakagawa, H.
Witte, J. S.
Eeles, R. A.
Kote-Jarai, Z.
Haiman, C. A.
Affiliation
Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.Issue Date
2021
Metadata
Show full item recordAbstract
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.Citation
Conti DV, Darst BF, Moss LC, Saunders EJ, Sheng X, Chou A, et al. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction. Nat Genet. 2021;53(1):65-75.Journal
Nature GeneticsDOI
10.1038/s41588-020-00748-0PubMed ID
33398198Additional Links
https://dx.doi.org/10.1038/s41588-020-00748-0Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41588-020-00748-0
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