Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
Journal article
Dadaev, Tokhir, Saunders, Edward J., Newcombe, Paul J., Anokian, Ezequiel, Leongamornlert, Daniel A., Brook, Mark N., Cieza-Borrella, Clara, Mijuskovic, Martina, Wakerell, Sarah, Olama, Ali Amin Al, Schumacher, Fredrick R., Berndt, Sonja I., Benlloch, Sara, Ahmed, Mahbubl, Goh, Chee, Sheng, Xin, Zhang, Zhuo, Muir, Kenneth, Govindasami, Koveela, ... The PRACTICAL Consortium*. (2018). Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants. Nature Communications. 9(1), p. Article 2256. https://doi.org/10.1038/s41467-018-04109-8
Authors | Dadaev, Tokhir, Saunders, Edward J., Newcombe, Paul J., Anokian, Ezequiel, Leongamornlert, Daniel A., Brook, Mark N., Cieza-Borrella, Clara, Mijuskovic, Martina, Wakerell, Sarah, Olama, Ali Amin Al, Schumacher, Fredrick R., Berndt, Sonja I., Benlloch, Sara, Ahmed, Mahbubl, Goh, Chee, Sheng, Xin, Zhang, Zhuo, Muir, Kenneth, Govindasami, Koveela, Lophatananon, Artitaya, Stevens, Victoria L., Gapstur, Susan M., Carter, Brian D., Tangen, Catherine M., Goodman, Phyllis, Thompson, Ian M., Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Clements, Judith, Horvath, Lisa, Tilley, Wayne, Risbridger, Gail, Grönberg, 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, Hakansson, Niclas, West, Catharine, Dunning, Alison M., Burnet, Neil, Mucci, Lorelei, Giovannucci, Edward, Andriole, Gerald, Cussenot, Olivier, Cancel-Tassin, Géraldine, Koutros, Stella, Freeman, Laura E. Beane, 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, Kerns, Sarah, 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, Fachal, Laura, 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., Weisher, 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, Slavov, Chavdar, Mitev, Vanio, Parliament, Matthew, Singhal, Sandeep, Claessens, Frank, Joniau, Steven, Van den Broeck, Thomas, Larkin, Samantha, Townsend, Paul A., Aukim-Hastie, Claire, Gago-Dominguez, Manuela, 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, Kierzek, Andrzej, Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., Lindström, 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., Kraft, Peter, Cook, Margaret, Thwaites, Alison, Guy, Michelle, Whitmore, Ian, Morgan, Angela, Fisher, Cyril, Hazel, Steve, Livni, Naomi, Spurdle, Amanda, Srinivasan, Srilakshmi, Kedda, Mary-Anne, Aitken, Joanne, Gardiner, Robert, Hayes, Vanessa, Butler, Lisa, Taylor, Renea, Yeadon, Trina, Eckert, Allison, Saunders, Pamela, Haynes, Anne-Maree, Papargiris, Melissa, Kujala, Paula, Talala, Kirsi, Murtola, Teemu, Taari, Kimmo, Dearnaley, David, Barnett, Gill, Bentzen, Søren, Elliott, Rebecca, Ranu, Hardeep, Hicks, Belynda, Vogt, Aurelie, Hutchinson, Amy, Cox, Angela, Davis, Michael, Brown, Paul, George, Anne, Marsden, Gemma, Lane, Athene, Lewis, Sarah J., Berry, Clare, Kulkarni, Girish S., Toi, Ants, Evans, Andrew, Zlotta, Alexandre R., van der Kwast, Theodorus H., Imai, Takashi, Saito, Shiro, Marzec, Jacek, Cao, Guangwen, Lin, Ji, Ling, Jin, Li, Meiling, Zhao, Shan-Chao, Ren, Guoping, Yu, Yongwei, Wu, Yudong, Wu, Ji, Zhou, Bo, Zhang, Yangling, Li, Jie, He, Weiyang, Guo, Jianming, Pedersen, John, Hopper, John L., Milne, Roger, Klim, Aleksandra, Carballo, Ana, Lobato-Busto, Ramón, Peleteiro, Paula, Calvo, Patricia, Aguado, Miguel, Ruiz-Dominguez, José Manuel, Cecchini, Lluís, Mengual, Lourdes, Alcaraz, Antonio, Bustamante, Mariona, Gracia-Lavedan, Esther, Dierssen-Sotos, Trinidad, Gómez Acebo, Inés, Pow-Sang, Julio, Park, Hyun, Zachariah, Babu, Kluzniak, Wojciech, Kolb, Suzanne, Klarskov, Peter, Stegmaier, Christa, Vogel, Walther, Herkommer, Kathleen, Bohnert, Philipp, Maia, Sofia, Silva, Maria P., De Langhe, Sofie, Thierens, Hubert, Tan, Meng H., Ong, Aik T., Kastelan, Zeljko, Popov, Elenko, Kachakova, Darina, Mitkova, Atanaska, Vlahova, Aleksandrina, Dikov, Tihomir, Christova, Svetlana, Carracedo, Angel, Bangma, Christopher, Schroder, F. H., Cenee, Sylvie, Tretarre, Brigitte, Rebillard, Xavier, Mulot, Claire, Sanchez, Marie, Adolfsson, Jan, Stattin, Par, Johansson, Jan-Erik, Cavalli-Bjoerkman, Carin, Karlsson, Ami, Broms, Michael, Wu, Huihai and The PRACTICAL Consortium* |
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Abstract | Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. |
Year | 2018 |
Journal | Nature Communications |
Journal citation | 9 (1), p. Article 2256 |
Publisher | Nature Publishing Group |
ISSN | 2041-1723 |
Digital Object Identifier (DOI) | https://doi.org/10.1038/s41467-018-04109-8 |
PubMed ID | 29892050 |
Scopus EID | 2-s2.0-85048420948 |
PubMed Central ID | PMC5995836 |
Open access | Published as ‘gold’ (paid) open access |
Research or scholarly | Research |
Page range | 1-19 |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 11 Jun 2018 |
Publication process dates | |
Accepted | 05 Apr 2018 |
Deposited | 09 Feb 2022 |
Additional information | *Please see the article for the full list of The PRACTICAL Consortium members. |
https://acuresearchbank.acu.edu.au/item/8x556/fine-mapping-of-prostate-cancer-susceptibility-loci-in-a-large-meta-analysis-identifies-candidate-causal-variants
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Publisher's version
OA_Dadaev_2018_Fine-mapping_of_prostate_cancer_susceptibility.pdf | |
License: CC BY 4.0 | |
File access level: Open |
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