Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
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Author
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
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
Hakansson, Niclas
West, Catharine
Dunning, Alison M.
Burnet, Neil
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
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.
Lindstrom, Sara
Riboli, Elio
Siddiq, Afshan
Canzian, Federico
Kolonel, Laurence N.
Le Marchand, Loic
Hoover, Robert N.
Machiela, Mitchell J.
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
Gomez-Acebo, Ines
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
Tillmans, Lori
Riska, Shaun
Freedman, Matthew
Wiklund, Fredrik
Chanock, Stephen
Henderson, Brian E.
Easton, Douglas F.
Haiman, Christopher A.
Eeles, Rosalind A.
Conti, David V.
Kote-Jarai, Zsofia
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Published Version
https://doi.org/10.1038/s41467-018-04109-8Metadata
Show full item recordCitation
Dadaev, T., E. J. Saunders, P. J. Newcombe, E. Anokian, D. A. Leongamornlert, M. N. Brook, C. Cieza-Borrella, et al. 2018. “Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants.” Nature Communications 9 (1): 2256. doi:10.1038/s41467-018-04109-8. http://dx.doi.org/10.1038/s41467-018-04109-8.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995836/pdf/Terms of Use
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