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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Tokhir Dadaev, Edward J. Saunders, Paul J. Newcombe, Ezequiel Anokian, Daniel A. Leongamornlert, Mark N. Brook, Clara Cieza-Borrella, Martina Mijuskovic, Sarah Wakerell, Ali Amin Al Olama, Fredrick R. Schumacher, Sonja I. Berndt, Sara Benlloch, Mahbubl Ahmed, Chee Goh, Xin Sheng, Zhuo Zhang, Kenneth Muir, Koveela Govindasami, Artitaya Lophatananon, Victoria L. Stevens, Susan M. Gapstur, Brian D. Carter, Catherine M. Tangen, Phyllis Goodman, Ian M. Thompson, Jyotsna Batra, Suzanne Chambers, Leire Moya, Judith Clements, Lisa Horvath, Wayne Tilley, Gail 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 Hakansson, Catharine West, Alison M. Dunning, Neil Burnet, Lorelei Mucci, Edward Giovannucci, Gerald 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 Rosenstein, Sarah 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, Laura Fachal, 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 Weisher, 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, Chavdar Slavov, Vanio Mitev, Matthew Parliament, Sandeep Singhal, 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, Andrzej Kierzek, 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, Peter Kraft, , Matthew Freedman, Fredrik Wiklund, Stephen Chanock, Brian E. Henderson, Douglas F. Easton, Christopher A. Haiman, Rosalind A. Eeles, David V. Conti, Zsofia Kote-Jarai

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. More... »

PAGES

2256

References to SciGraph publications

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    1

    VOLUME

    9

    Author Affiliations

  • Institute of Cancer Research
  • University of Cambridge
  • Wellcome Sanger Institute
  • University Hospitals of Cleveland
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases
  • University of Southern California
  • University of Warwick
  • American Cancer Society
  • Fred Hutchinson Cancer Research Center
  • Christus Santa Rosa Hospital
  • Translational Research Institute
  • Cancer Council Queensland
  • Garvan Institute of Medical Research
  • University of Adelaide
  • Peter MacCallum Cancer Centre
  • Karolinska Institute
  • University College London
  • Turku University Hospital
  • University of Turku
  • University of Tampere
  • Cambridge University Hospitals NHS Foundation Trust
  • Harvard University
  • Washington University in St. Louis
  • Tenon Hospital
  • Aarhus University
  • Aarhus University Hospital
  • Oslo University Hospital
  • University of Oxford
  • University of Bristol
  • Princess Margaret Cancer Centre
  • Icahn School of Medicine at Mount Sinai
  • University of Rochester Medical Center
  • Albert Einstein College of Medicine
  • Queen Mary University of London
  • Second Military Medical University
  • Nanjing Medical University
  • Liaoning Provincial People's Hospital
  • Zhongshan Hospital
  • University of Melbourne
  • Monash University
  • University of Tasmania
  • Brigham and Women's Hospital
  • Complejo Hospitalario Universitario de Santiago
  • Pompeu Fabra University
  • University of Cantabria
  • Moffitt Cancer Center
  • Louisiana State University Health Sciences Center New Orleans
  • University of Washington
  • Pomeranian Medical University
  • National Human Genome Research Institute
  • University of Copenhagen
  • German Cancer Research Center
  • Krebsregister Saarland
  • University Hospital Ulm
  • The University of Texas MD Anderson Cancer Center
  • Stanford University
  • University of Porto
  • City Of Hope National Medical Center
  • Ghent University
  • Ghent University Hospital
  • University of Malaya
  • Subang Jaya Medical Centre
  • University Medical Center Hamburg-Eppendorf
  • University Hospital Centre Zagreb
  • Medical University of Sofia
  • University of Alberta
  • KU Leuven
  • Universitaire Ziekenhuizen Leuven
  • University of Manchester
  • University of Surrey
  • University of California, San Diego
  • University Hospital Complex Of Vigo
  • Erasmus University Medical Center
  • University of Paris-Sud
  • NorthShore University HealthSystem
  • George E. Wahlen Department of VA Medical Center
  • Mayo Clinic
  • Imperial College London
  • University of Hawaii at Manoa
  • Dana–Farber Cancer Institute
  • Royal Marsden NHS Foundation Trust
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41467-018-04109-8

    DOI

    http://dx.doi.org/10.1038/s41467-018-04109-8

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1104381151

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29892050


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