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dc.contributor.authorGusev, Alexanderen
dc.contributor.authorShi, Huwenboen
dc.contributor.authorKichaev, Gleben
dc.contributor.authorPomerantz, Marken
dc.contributor.authorLi, Fugenen
dc.contributor.authorLong, Henry Wen
dc.contributor.authorIngles, Sue Aen
dc.contributor.authorKittles, Rick Aen
dc.contributor.authorStrom, Sara Sen
dc.contributor.authorRybicki, Benjamin Aen
dc.contributor.authorNemesure, Barbaraen
dc.contributor.authorIsaacs, William Ben
dc.contributor.authorZheng, Weien
dc.contributor.authorPettaway, Curtis Aen
dc.contributor.authorYeboah, Edward Den
dc.contributor.authorTettey, Yaoen
dc.contributor.authorBiritwum, Richard Ben
dc.contributor.authorAdjei, Andrew Aen
dc.contributor.authorTay, Evelynen
dc.contributor.authorTruelove, Annen
dc.contributor.authorNiwa, Shelleyen
dc.contributor.authorChokkalingam, Anand Pen
dc.contributor.authorJohn, Esther Men
dc.contributor.authorMurphy, Adam Ben
dc.contributor.authorSignorello, Lisa Ben
dc.contributor.authorCarpten, Johnen
dc.contributor.authorLeske, M Cristinaen
dc.contributor.authorWu, Suh-Yuhen
dc.contributor.authorHennis, Anslem JMen
dc.contributor.authorNeslund-Dudas, Christineen
dc.contributor.authorHsing, Ann Wen
dc.contributor.authorChu, Lisaen
dc.contributor.authorGoodman, Phyllis Jen
dc.contributor.authorKlein, Eric Aen
dc.contributor.authorWitte, John Sen
dc.contributor.authorCasey, Grahamen
dc.contributor.authorKaggwa, Samen
dc.contributor.authorCook, Michael Ben
dc.contributor.authorStram, Daniel Oen
dc.contributor.authorBlot, William Jen
dc.contributor.authorEeles, Rosalind Aen
dc.contributor.authorEaston, Douglasen
dc.contributor.authorKote-Jarai, ZSofiaen
dc.contributor.authorAmin Al Olama, Alien
dc.contributor.authorBenlloch, Saraen
dc.contributor.authorMuir, Kennethen
dc.contributor.authorGiles, Graham Gen
dc.contributor.authorSouthey, Melissa Cen
dc.contributor.authorFitzgerald, Liesel Men
dc.contributor.authorGronberg, Henriken
dc.contributor.authorWiklund, Fredriken
dc.contributor.authorAly, Markusen
dc.contributor.authorHenderson, Brian Een
dc.contributor.authorSchleutker, Johannaen
dc.contributor.authorWahlfors, Tiinaen
dc.contributor.authorTammela, Teuvo LJen
dc.contributor.authorNordestgaard, Børge Gen
dc.contributor.authorKey, Tim Jen
dc.contributor.authorTravis, Ruth Cen
dc.contributor.authorNeal, David Een
dc.contributor.authorDonovan, Jenny Len
dc.contributor.authorHamdy, Freddie Cen
dc.contributor.authorPharoah, Paulen
dc.contributor.authorPashayan, Noraen
dc.contributor.authorKhaw, Kay-Teeen
dc.contributor.authorStanford, Janet Len
dc.contributor.authorThibodeau, Stephen Nen
dc.contributor.authorMcDonnell, Shannon Ken
dc.contributor.authorSchaid, Daniel Jen
dc.contributor.authorMaier, Christianeen
dc.contributor.authorVogel, Waltheren
dc.contributor.authorLuedeke, Manuelen
dc.contributor.authorHerkommer, Kathleenen
dc.contributor.authorKibel, Adam Sen
dc.contributor.authorCybulski, Cezaryen
dc.contributor.authorWokolorczyk, Dominikaen
dc.contributor.authorKluzniak, Wojciechen
dc.contributor.authorCannon-Albright, Lisaen
dc.contributor.authorTeerlink, Craigen
dc.contributor.authorBrenner, Hermannen
dc.contributor.authorDieffenbach, Aida Ken
dc.contributor.authorArndt, Volkeren
dc.contributor.authorPark, Jong Yen
dc.contributor.authorSellers, Thomas Aen
dc.contributor.authorLin, Hui-Yien
dc.contributor.authorSlavov, Chavdaren
dc.contributor.authorKaneva, Radkaen
dc.contributor.authorMitev, Vanioen
dc.contributor.authorBatra, Jyotsnaen
dc.contributor.authorSpurdle, Amandaen
dc.contributor.authorClements, Judith Aen
dc.contributor.authorTeixeira, Manuel Ren
dc.contributor.authorPandha, Hardeven
dc.contributor.authorMichael, Agnieszkaen
dc.contributor.authorPaulo, Paulaen
dc.contributor.authorMaia, Sofiaen
dc.contributor.authorKierzek, Andrzejen
dc.contributor.authorThe, PRACTICAL consortiumen
dc.contributor.authorConti, David Ven
dc.contributor.authorAlbanes, Demetriusen
dc.contributor.authorBerg, Christineen
dc.contributor.authorBerndt, Sonja Ien
dc.contributor.authorCampa, Danieleen
dc.contributor.authorCrawford, E Daviden
dc.contributor.authorDiver, W Ryanen
dc.contributor.authorGapstur, Susan Men
dc.contributor.authorGaziano, J Michaelen
dc.contributor.authorGiovannucci, Edwarden
dc.contributor.authorHoover, Roberten
dc.contributor.authorHunter, David Jen
dc.contributor.authorJohansson, Mattiasen
dc.contributor.authorKraft, Peteren
dc.contributor.authorLe, Marchand Loicen
dc.contributor.authorLindström, Saraen
dc.contributor.authorNavarro, Carmenen
dc.contributor.authorOvervad, Kimen
dc.contributor.authorRiboli, Elioen
dc.contributor.authorSiddiq, Afshanen
dc.contributor.authorStevens, Victoria Len
dc.contributor.authorTrichopoulos, Dimitriosen
dc.contributor.authorVineis, Paoloen
dc.contributor.authorYeager, Meredithen
dc.contributor.authorTrynka, Gosiaen
dc.contributor.authorRaychaudhuri, Soumyaen
dc.contributor.authorSchumacher, Frederick Ren
dc.contributor.authorPrice, Alkes Len
dc.contributor.authorFreedman, Matthew Len
dc.contributor.authorHaiman, Christopher Aen
dc.contributor.authorPasaniuc, Bogdanen
dc.date.accessioned2016-08-03T16:40:22Z
dc.date.available2016-08-03T16:40:22Z
dc.date.issued2016-04-07en
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/256968
dc.description.abstractAlthough genome-wide association studies have identified over 100 risk loci that explain ~33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.
dc.description.sponsorshipThis work was supported by NIH fellowship F32 GM106584 (AG), NIH grants R01 MH101244(A.G.), R01 CA188392 (B.P.), U01 CA194393(B.P.), R01 GM107427 (M.L.F.), R01 CA193910 (M.L.F./M.P.) and Prostate Cancer Foundation Challenge Award (M.L.F./M.P.). This study makes use of data generated by the Wellcome Trust Case Control Consortium and the Wellcome Trust Sanger Institute. A full list of the investigators who contributed to the generation of the Wellcome Trust Case Control Consortium data is available on www.wtccc.org.uk. Funding for the Wellcome Trust Case Control Consortium project was provided by the Wellcome Trust under award 076113. This study makes use of data generated by the UK10K Consortium. A full list of the investigators who contributed to the generation of the data is available online (http://www.UK10K.org). The PRACTICAL consortium was supported by the following grants: European Commission's Seventh Framework Programme grant agreement n° 223175 (HEALTH-F2-2009-223175), Cancer Research UK Grants C5047/A7357, C1287/A10118, C5047/A3354, C5047/A10692, C16913/A6135 and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative Grant: no. 1 U19 CA 148537-01 (the GAME-ON initiative); Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007 and C5047/A10692), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112—the GAME-ON initiative), the Department of Defense (W81XWH-10-1-0341), A Linneus Centre (Contract ID 70867902), Swedish Research Council (grant no K2010-70X-20430-04-3), the Swedish Cancer Foundation (grant no 09-0677), grants RO1CA056678, RO1CA082664 and RO1CA092579 from the US National Cancer Institute, National Institutes of Health; US National Cancer Institute (R01CA72818); support from The National Health and Medical Research Council, Australia (126402, 209057, 251533, 396414, 450104, 504700, 504702, 504715, 623204, 940394 and 614296); NIH grants CA63464, CA54281 and CA098758; US National Cancer Institute (R01CA128813, PI: J.Y. Park); Bulgarian National Science Fund, Ministry of Education and Science (contract DOO-119/2009; DUNK01/2–2009; DFNI-B01/28/2012); Cancer Research UK grants [C8197/A10123] and [C8197/A10865]; grant code G0500966/75466; NIHR Health Technology Assessment Programme (projects 96/20/06 and 96/20/99); Cancer Research UK grant number C522/A8649, Medical Research Council of England grant number G0500966, ID 75466 and The NCRI, UK; The US Dept of Defense award W81XWH-04-1-0280; Australia Project Grant [390130, 1009458] and Enabling Grant [614296 to APCB]; the Prostate Cancer Foundation of Australia (Project Grant [PG7] and Research infrastructure grant [to APCB]); NIH grant R01 CA092447; Vanderbilt-Ingram Cancer Center (P30 CA68485); Cancer Research UK [C490/A10124] and supported by the UK National Institute for Health Research Biomedical Research Centre at the University of Cambridge; Competitive Research Funding of the Tampere University Hospital (9N069 and X51003); Award Number P30CA042014 from the National Cancer Institute.
dc.languageEnglishen
dc.language.isoenen
dc.publisherNature Publishing Group
dc.rightsAttribution 4.0 International*
dc.rightsAttribution 4.0 Internationalen
dc.rightsAttribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectbiological sciencesen
dc.subjectcanceren
dc.subjectgeneticsen
dc.titleAtlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulationen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/0.1038/ncomms10979en
prism.number10979en
prism.publicationDate2016en
prism.publicationNameNature Communicationsen
prism.volume7en
dc.identifier.doi10.17863/CAM.900
dcterms.dateAccepted2016-02-03en
rioxxterms.versionofrecord10.1038/ncomms10979en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2016-04-07en
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.contributor.orcidAmin Al Olama, Ali [0000-0002-7178-3431]
dc.contributor.orcidPharoah, Paul [0000-0001-8494-732X]
dc.contributor.orcidKhaw, Kay-Tee [0000-0002-8802-2903]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (G0500966)
pubs.funder-project-idNational Cancer Institute (NCI) (R01CA128978)
pubs.funder-project-idNational Cancer Institute (NCI) (U19CA148537)
pubs.funder-project-idNational Cancer Institute (NCI) (U19CA148065)
pubs.funder-project-idMEDICAL RESEARCH COUNCIL (MR/N003284/1)
pubs.funder-project-idMRC (G0401527)
pubs.funder-project-idEC FP7 CP (223175)
pubs.funder-project-idCancer Research UK (CRUK-A10710)
pubs.funder-project-idCancer Research UK (CRUK-A12014)
pubs.funder-project-idCancer Research UK (CRUK-A10118)
pubs.funder-project-idCancer Research UK (A10123)
pubs.funder-project-idCancer Research UK (A8649)
cam.orpheus.successThu Jan 30 12:57:21 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International