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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans
Human Molecular Genetics, Volume 24, No. 19, Year 2015
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Description
Genome-wide association studies (GWAS) have identified numerouscommon prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variationwas observed at 39 regions; 35 of which are nowdescribed by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-AsianGWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci nowexplain ~38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reportedGWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same region. © The Author 2015. Published by Oxford University Press. All rights reserved.
Authors & Co-Authors
Al Olama, Ali Amin
United Kingdom, Cambridge
Strangeways Research Laboratory
Dadaev, Tokhir
United Kingdom, London
The Institute of Cancer Research
Hazelett, Dennis J.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Leongamornlert, Daniel A.
United Kingdom, London
The Institute of Cancer Research
Saunders, Edward J.
United Kingdom, London
The Institute of Cancer Research
Giles, Graham G.
Australia, East Melbourne
Cancer Council Victoria
Australia, Melbourne
Melbourne School of Population and Global Health
Southey, Melissa Caroline
Australia, Melbourne
University of Melbourne
FitzGerald, Liesel M.
Australia, Mount Waverley
Tissupath Pty Ltd.
Grönberg, Henrik
Sweden, Stockholm
Karolinska Institutet
Wiklund, Fredrik E.
Sweden, Stockholm
Karolinska Institutet
Aly, Markus
Sweden, Stockholm
Karolinska Institutet
Sweden, Danderyd
Danderyds Sjukhus
Henderson, Brian E.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Schumacher, Fredrick R.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Haiman, Christopher A.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Schleutker, Johanna
Finland, Turku
Turun Yliopisto
Finland, Tampere
Fimlab Laboratoriot oy
Wahlfors, Tiina A.
Finland, Tampere
Fimlab Laboratoriot oy
Tammela, Teuvo L.J.
Finland, Tampere
Tampere University
Nordestgaard, BØrge Grønne
Denmark, Copenhagen
Copenhagen University Hospital
Denmark, Copenhagen
Københavns Universitet
Key, Timothy J.
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Travis, Ruth C.
United Kingdom, Oxford
University of Oxford Medical Sciences Division
Neal, David E.
United Kingdom, Cambridge
Addenbrooke's Hospital
United Kingdom, Cambridge
Cancer Research uk Cambridge Institute
Donovan, Jenny L.
United Kingdom, Bristol
University of Bristol
Hamdy, Freddie Charles
United Kingdom, Oxford
University of Oxford Medical Sciences Division
United Kingdom, Oxford
John Radcliffe Hospital
Pharoah, Paul D.P.
United Kingdom, Cambridge
Strangeways Research Laboratory
Pashayan, Nora
United Kingdom, Cambridge
Strangeways Research Laboratory
United Kingdom, London
University College London
Khaw, Kay Tee T.
United Kingdom, Cambridge
University of Cambridge
Stanford, Janet L.
United States, Seattle
Fred Hutchinson Cancer Center
United States, Seattle
University of Washington
Thibodeau, Stephen N.
United States, Rochester
Mayo Clinic
McDonnell, Shannon K.
United States, Rochester
Mayo Clinic
Schaid, Daniel J.
United States, Rochester
Mayo Clinic
Maier, Christiane
Germany, Ulm
Universitätsklinikum Ulm
Vogel, Walther
Germany, Ulm
Universität Ulm
Luedeke, Manuel
Germany, Ulm
Universitätsklinikum Ulm
Herkommer, Kathleen
Germany, Munich
Technische Universität München
Kibel, Adam S.
United States, Boston
Dana-farber Cancer Institute
Cybulski, Cezary
Poland, Szczecin
Pomeranian Medical University in Szczecin
Wokołorczyk, Dominika
Poland, Szczecin
Pomeranian Medical University in Szczecin
Kluzńiak, Wojciech
Poland, Szczecin
Pomeranian Medical University in Szczecin
Cannon-Albright, Lisa Anne
United States, Salt Lake City
University of Utah School of Medicine
United States
Va Medical Center
Brenner, Hermann
Germany, Heidelberg
German Cancer Research Center
Arndt, Volker
Germany, Heidelberg
German Cancer Research Center
Park, Jong-yun
Unknown Affiliation
Sellers, Thomas
Unknown Affiliation
Lin, Huiyi
United States, Tampa
Moffitt Cancer Center
Slavov, Ch K.
Bulgaria, Sofia
Medical University of Sofia
Kaneva, Radka
Bulgaria, Sofia
Medical University of Sofia
Mitev, Vanio Ivanov
Bulgaria, Sofia
Medical University of Sofia
Batra, Jyotsna
Australia, Brisbane
Australian Prostate Cancer Research Centre – Queensland
Clements, Judith Ann
Australia, Brisbane
Australian Prostate Cancer Research Centre – Queensland
Spurdle, Amanda B.
Australia, Brisbane
Qimr Berghofer Medical Research Institute
Teixeira, Manuel Rodrigues
Portugal, Porto
Instituto Português de Oncologia do Porto fg
Portugal, Porto
Universidade do Porto
Paulo, Paula
Portugal, Porto
Instituto Português de Oncologia do Porto fg
Maia, Sofia F.
Portugal, Porto
Instituto Português de Oncologia do Porto fg
Pandha, Hardev S.
United Kingdom, Guildford
University of Surrey
Michael, Agnieszka
United Kingdom, Guildford
University of Surrey
Kierzek, Andrzej M.
United Kingdom, Guildford
University of Surrey
Govindasami, Koveela
United Kingdom, London
The Institute of Cancer Research
Guy, Michelle
United Kingdom, London
The Institute of Cancer Research
Muir, Kenneth Ross
United Kingdom, Manchester
The University of Manchester
United Kingdom, Coventry
University of Warwick
Viñuela, Ana
United Kingdom, London
King's College London
Brown, Andrew Anand
Norway, Oslo
Universitetet I Oslo
Switzerland, Geneva
Université de Genève
Freedman, Matthew Lee
United States, Boston
Dana-farber Cancer Institute
Conti, David V.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Easton, Douglas F.
United Kingdom, Cambridge
Strangeways Research Laboratory
Coetzee, Gerhard A.
United States, Los Angeles
Usc Norris Comprehensive Cancer Center
Eeles, Rosalind A.
United Kingdom, London
The Institute of Cancer Research
Kóte-Jarai, Zsofia S.
United Kingdom, London
The Institute of Cancer Research
Statistics
Citations: 59
Authors: 67
Affiliations: 45
Identifiers
Doi:
10.1093/hmg/ddv203
ISSN:
09646906
Research Areas
Cancer