Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Dadaev, Tokhir and Saunders, Edward J. and Newcombe, Paul J. and Anokian, Ezequiel and Leongamornlert, Daniel A. and Brook, Mark N. and Cieza-Borrella, Clara and Mijuskovic, Martina and Wakerell, Sarah and Olama, Ali Amin Al and Schumacher, Fredrick R. and Berndt, Sonja I. and Benlloch, Sara and Ahmed, Mahbubl and Goh, Chee and Sheng, Xin and Zhang, Zhuo and Muir, Kenneth and Govindasami, Koveela and Lophatananon, Artitaya and Stevens, Victoria L. and Gapstur, Susan M. and Carter, Brian D. and Tangen, Catherine M. and Goodman, Phyllis and Thompson, Ian M. and Batra, Jyotsna and Chambers, Suzanne and Moya, Leire and Clements, Judith and Horvath, Lisa and Tilley, Wayne and Risbridger, Gail and Gronberg, Henrik and Aly, Markus and Nordström, Tobias and Pharoah, Paul and Pashayan, Nora and Schleutker, Johanna and Tammela, Teuvo L. J. and Sipeky, Csilla and Auvinen, Anssi and Albanes, Demetrius and Weinstein, Stephanie and Wolk, Alicja and Hakansson, Niclas and West, Catharine and Dunning, Alison M. and Burnet, Neil and Mucci, Lorelei and Giovannucci, Edward and Andriole, Gerald and Cussenot, Olivier and Cancel-Tassin, Géraldine and Koutros, Stella and Freeman, Laura E. Beane and Sorensen, Karina Dalsgaard and Orntoft, Torben Falck and Borre, Michael and Maehle, Lovise 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 Finelli, Antonio and Ingles, Sue Ann and Stern, Mariana C. and Rosenstein, Barry and Kerns, Sarah and Ostrer, Harry and Lu, Yong-Jie and Zhang, Hong-Wei and Feng, Ninghan and Mao, Xueying and Guo, Xin and Wang, Guomin and Sun, Zan 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 Vega, Ana and Gómez-Caamaño, Antonio and Fachal, Laura and Szulkin, Robert and Eklund, Martin and Kogevinas, Manolis and Llorca, Javier and Castaño-Vinyals, Gemma and Penney, Kathryn L. and Stampfer, Meir and Park, Jong Y. and Sellers, Thomas A. and Lin, Hui-Yi and Stanford, Janet L. and Cybulski, Cezary and Wokolorczyk, Dominika and Lubinski, Jan and Ostrander, Elaine A. and Geybels, Milan S. and Nordestgaard, Børge G. and Nielsen, Sune F. and Weisher, Maren and Bisbjerg, Rasmus and Røder, Martin Andreas and Iversen, Peter and Brenner, Hermann and Cuk, Katarina and Holleczek, Bernd and Maier, Christiane and Luedeke, Manuel and Schnoeller, Thomas and Kim, Jeri and Logothetis, Christopher J. and John, Esther M. and Teixeira, Manuel R. and Paulo, Paula and Cardoso, Marta and Neuhausen, Susan L. and Steele, Linda and Ding, Yuan Chun and De Ruyck, Kim and De Meerleer, Gert and Ost, Piet and Razack, Azad and Lim, Jasmine and Teo, Soo-Hwang and Lin, Daniel W. and Newcomb, Lisa F. and Lessel, Davor and Gamulin, Marija and Kuliš, Tomislav and Kaneva, Radka and Usmani, Nawaid and Slavov, Chavdar and Mitev, Vanio and Parliament, Matthew and Singhal, Sandeep and Claessens, Frank and Joniau, Steven and Van den Broeck, Thomas and Larkin, Samantha and Townsend, Paul A. and Aukim-Hastie, Claire and Gago-Dominguez, Manuela and Castelao, Jose Esteban and Martinez, Maria Elena and Roobol, Monique J. and Jenster, Guido and van Schaik, Ron H. N. and Menegaux, Florence and Truong, Thérèse and Koudou, Yves Akoli and Xu, Jianfeng and Khaw, Kay-Tee and Cannon-Albright, Lisa and Pandha, Hardev and Michael, Agnieszka and Kierzek, Andrzej and Thibodeau, Stephen N. and McDonnell, Shannon K. and Schaid, Daniel J. and Lindstrom, Sara and Turman, Constance and Ma, Jing and Hunter, David J. and Riboli, Elio and Siddiq, Afshan and Canzian, Federico and Kolonel, Laurence N. and Le Marchand, Loic and Hoover, Robert N. and Machiela, Mitchell J. and Kraft, Peter and Freedman, Matthew and Wiklund, Fredrik and Chanock, Stephen and Henderson, Brian E. and Easton, Douglas F. and Haiman, Christopher A. and Eeles, Rosalind A. and Conti, David V. and Kote-Jarai, Zsofia (2018) Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants. Nature Communications, 9 (2256). ISSN 2041-1723

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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.

Item Type: Article
Additional Information: Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2018
MeSH: African Continental Ancestry Group/genetics ; Algorithms ; Bayes Theorem ; Chromosome Mapping ; European Continental Ancestry Group/genetics ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Male ; Molecular Sequence Annotation ; Multivariate Analysis ; Polymorphism, Single Nucleotide ; Prostatic Neoplasms/genetics ; Quantitative Trait Loci ; Risk
Departments: Katedra za urologiju
Katedra za radiologiju i opću kliničku onkologiju
Depositing User: Kristina Berketa
Status: Published
Creators:
CreatorsEmail
Dadaev, TokhirUNSPECIFIED
Saunders, Edward J.UNSPECIFIED
Newcombe, Paul J.UNSPECIFIED
Anokian, EzequielUNSPECIFIED
Leongamornlert, Daniel A.UNSPECIFIED
Brook, Mark N.UNSPECIFIED
Cieza-Borrella, ClaraUNSPECIFIED
Mijuskovic, MartinaUNSPECIFIED
Wakerell, SarahUNSPECIFIED
Olama, Ali Amin AlUNSPECIFIED
Schumacher, Fredrick R.UNSPECIFIED
Berndt, Sonja I.UNSPECIFIED
Benlloch, SaraUNSPECIFIED
Ahmed, MahbublUNSPECIFIED
Goh, CheeUNSPECIFIED
Sheng, XinUNSPECIFIED
Zhang, ZhuoUNSPECIFIED
Muir, KennethUNSPECIFIED
Govindasami, KoveelaUNSPECIFIED
Lophatananon, ArtitayaUNSPECIFIED
Stevens, Victoria L.UNSPECIFIED
Gapstur, Susan M.UNSPECIFIED
Carter, Brian D.UNSPECIFIED
Tangen, Catherine M.UNSPECIFIED
Goodman, PhyllisUNSPECIFIED
Thompson, Ian M.UNSPECIFIED
Batra, JyotsnaUNSPECIFIED
Chambers, SuzanneUNSPECIFIED
Moya, LeireUNSPECIFIED
Clements, JudithUNSPECIFIED
Horvath, LisaUNSPECIFIED
Tilley, WayneUNSPECIFIED
Risbridger, GailUNSPECIFIED
Gronberg, HenrikUNSPECIFIED
Aly, MarkusUNSPECIFIED
Nordström, TobiasUNSPECIFIED
Pharoah, PaulUNSPECIFIED
Pashayan, NoraUNSPECIFIED
Schleutker, JohannaUNSPECIFIED
Tammela, Teuvo L. J.UNSPECIFIED
Sipeky, CsillaUNSPECIFIED
Auvinen, AnssiUNSPECIFIED
Albanes, DemetriusUNSPECIFIED
Weinstein, StephanieUNSPECIFIED
Wolk, AlicjaUNSPECIFIED
Hakansson, NiclasUNSPECIFIED
West, CatharineUNSPECIFIED
Dunning, Alison M.UNSPECIFIED
Burnet, NeilUNSPECIFIED
Mucci, LoreleiUNSPECIFIED
Giovannucci, EdwardUNSPECIFIED
Andriole, GeraldUNSPECIFIED
Cussenot, OlivierUNSPECIFIED
Cancel-Tassin, GéraldineUNSPECIFIED
Koutros, StellaUNSPECIFIED
Freeman, Laura E. BeaneUNSPECIFIED
Sorensen, Karina DalsgaardUNSPECIFIED
Orntoft, Torben FalckUNSPECIFIED
Borre, MichaelUNSPECIFIED
Maehle, LoviseUNSPECIFIED
Grindedal, Eli MarieUNSPECIFIED
Neal, David E.UNSPECIFIED
Donovan, Jenny L.UNSPECIFIED
Hamdy, Freddie C.UNSPECIFIED
Martin, Richard M.UNSPECIFIED
Travis, Ruth C.UNSPECIFIED
Key, Tim J.UNSPECIFIED
Hamilton, Robert J.UNSPECIFIED
Fleshner, Neil E.UNSPECIFIED
Finelli, AntonioUNSPECIFIED
Ingles, Sue AnnUNSPECIFIED
Stern, Mariana C.UNSPECIFIED
Rosenstein, BarryUNSPECIFIED
Kerns, SarahUNSPECIFIED
Ostrer, HarryUNSPECIFIED
Lu, Yong-JieUNSPECIFIED
Zhang, Hong-WeiUNSPECIFIED
Feng, NinghanUNSPECIFIED
Mao, XueyingUNSPECIFIED
Guo, XinUNSPECIFIED
Wang, GuominUNSPECIFIED
Sun, ZanUNSPECIFIED
Giles, Graham G.UNSPECIFIED
Southey, Melissa C.UNSPECIFIED
MacInnis, Robert J.UNSPECIFIED
FitzGerald, Liesel M.UNSPECIFIED
Kibel, Adam S.UNSPECIFIED
Drake, Bettina F.UNSPECIFIED
Vega, AnaUNSPECIFIED
Gómez-Caamaño, AntonioUNSPECIFIED
Fachal, LauraUNSPECIFIED
Szulkin, RobertUNSPECIFIED
Eklund, MartinUNSPECIFIED
Kogevinas, ManolisUNSPECIFIED
Llorca, JavierUNSPECIFIED
Castaño-Vinyals, GemmaUNSPECIFIED
Penney, Kathryn L.UNSPECIFIED
Stampfer, MeirUNSPECIFIED
Park, Jong Y.UNSPECIFIED
Sellers, Thomas A.UNSPECIFIED
Lin, Hui-YiUNSPECIFIED
Stanford, Janet L.UNSPECIFIED
Cybulski, CezaryUNSPECIFIED
Wokolorczyk, DominikaUNSPECIFIED
Lubinski, JanUNSPECIFIED
Ostrander, Elaine A.UNSPECIFIED
Geybels, Milan S.UNSPECIFIED
Nordestgaard, Børge G.UNSPECIFIED
Nielsen, Sune F.UNSPECIFIED
Weisher, MarenUNSPECIFIED
Bisbjerg, RasmusUNSPECIFIED
Røder, Martin AndreasUNSPECIFIED
Iversen, PeterUNSPECIFIED
Brenner, HermannUNSPECIFIED
Cuk, KatarinaUNSPECIFIED
Holleczek, BerndUNSPECIFIED
Maier, ChristianeUNSPECIFIED
Luedeke, ManuelUNSPECIFIED
Schnoeller, ThomasUNSPECIFIED
Kim, JeriUNSPECIFIED
Logothetis, Christopher J.UNSPECIFIED
John, Esther M.UNSPECIFIED
Teixeira, Manuel R.UNSPECIFIED
Paulo, PaulaUNSPECIFIED
Cardoso, MartaUNSPECIFIED
Neuhausen, Susan L.UNSPECIFIED
Steele, LindaUNSPECIFIED
Ding, Yuan ChunUNSPECIFIED
De Ruyck, KimUNSPECIFIED
De Meerleer, GertUNSPECIFIED
Ost, PietUNSPECIFIED
Razack, AzadUNSPECIFIED
Lim, JasmineUNSPECIFIED
Teo, Soo-HwangUNSPECIFIED
Lin, Daniel W.UNSPECIFIED
Newcomb, Lisa F.UNSPECIFIED
Lessel, DavorUNSPECIFIED
Gamulin, MarijaUNSPECIFIED
Kuliš, TomislavUNSPECIFIED
Kaneva, RadkaUNSPECIFIED
Usmani, NawaidUNSPECIFIED
Slavov, ChavdarUNSPECIFIED
Mitev, VanioUNSPECIFIED
Parliament, MatthewUNSPECIFIED
Singhal, SandeepUNSPECIFIED
Claessens, FrankUNSPECIFIED
Joniau, StevenUNSPECIFIED
Van den Broeck, ThomasUNSPECIFIED
Larkin, SamanthaUNSPECIFIED
Townsend, Paul A.UNSPECIFIED
Aukim-Hastie, ClaireUNSPECIFIED
Gago-Dominguez, ManuelaUNSPECIFIED
Castelao, Jose EstebanUNSPECIFIED
Martinez, Maria ElenaUNSPECIFIED
Roobol, Monique J.UNSPECIFIED
Jenster, GuidoUNSPECIFIED
van Schaik, Ron H. N.UNSPECIFIED
Menegaux, FlorenceUNSPECIFIED
Truong, ThérèseUNSPECIFIED
Koudou, Yves AkoliUNSPECIFIED
Xu, JianfengUNSPECIFIED
Khaw, Kay-TeeUNSPECIFIED
Cannon-Albright, LisaUNSPECIFIED
Pandha, HardevUNSPECIFIED
Michael, AgnieszkaUNSPECIFIED
Kierzek, AndrzejUNSPECIFIED
Thibodeau, Stephen N.UNSPECIFIED
McDonnell, Shannon K.UNSPECIFIED
Schaid, Daniel J.UNSPECIFIED
Lindstrom, SaraUNSPECIFIED
Turman, ConstanceUNSPECIFIED
Ma, JingUNSPECIFIED
Hunter, David J.UNSPECIFIED
Riboli, ElioUNSPECIFIED
Siddiq, AfshanUNSPECIFIED
Canzian, FedericoUNSPECIFIED
Kolonel, Laurence N.UNSPECIFIED
Le Marchand, LoicUNSPECIFIED
Hoover, Robert N.UNSPECIFIED
Machiela, Mitchell J.UNSPECIFIED
Kraft, PeterUNSPECIFIED
Freedman, MatthewUNSPECIFIED
Wiklund, FredrikUNSPECIFIED
Chanock, StephenUNSPECIFIED
Henderson, Brian E.UNSPECIFIED
Easton, Douglas F.UNSPECIFIED
Haiman, Christopher A.UNSPECIFIED
Eeles, Rosalind A.UNSPECIFIED
Conti, David V.UNSPECIFIED
Kote-Jarai, ZsofiaUNSPECIFIED
Date: 11 June 2018
Date Deposited: 19 Jul 2019 09:18
Last Modified: 19 Jul 2019 09:18
Subjects: /
Related URLs:
URI: http://medlib.mef.hr/id/eprint/3298

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