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dc.contributor.authorZuber, Ven_US
dc.contributor.authorBettella, Fen_US
dc.contributor.authorWitoelar, Aen_US
dc.contributor.authorPRACTICAL Consortiumen_US
dc.contributor.authorCRUK GWASen_US
dc.contributor.authorBCAC Consortiumen_US
dc.contributor.authorTRICL Consortiumen_US
dc.contributor.authorAndreassen, OAen_US
dc.contributor.authorMills, IGen_US
dc.contributor.authorUrbanucci, Aen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2019-02-20T12:01:55Z
dc.date.issued2017-03-31en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/28359301en_US
dc.identifier10.1186/s12864-017-3620-yen_US
dc.identifier.citationBMC Genomics, 2017, 18 (1), pp. 270 - ?en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3078
dc.identifier.eissn1471-2164en_US
dc.identifier.doi10.1186/s12864-017-3620-yen_US
dc.description.abstractBACKGROUND: Epigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA elements, acting to determine tissue or cell identity and driving tumor progression. Although previous approaches have been tried to explain risk associated with SNPs in regulatory DNA elements, so far epigenetic readers such as bromodomain containing protein 4 (BRD4) and super-enhancers have not been used to annotate SNPs. In prostate cancer (PC), androgen receptor (AR) binding sites to chromatin have been used to inform functional annotations of SNPs. RESULTS: Here we establish criteria for enhancer mapping which are applicable to other diseases and traits to achieve the optimal tissue-specific enrichment of PC risk SNPs. We used stratified Q-Q plots and Fisher test to assess the differential enrichment of SNPs mapping to specific categories of enhancers. We find that BRD4 is the key discriminant of tissue-specific enhancers, showing that it is more powerful than AR binding information to capture PC specific risk loci, and can be used with similar effect in breast cancer (BC) and applied to other diseases such as schizophrenia. CONCLUSIONS: This is the first study to evaluate the enrichment of epigenetic readers in genome-wide associations studies for SNPs within enhancers, and provides a powerful tool for enriching and prioritizing PC and BC genetic risk loci. Our study represents a proof of principle applicable to other diseases and traits that can be used to redefine molecular mechanisms of human phenotypic variation.en_US
dc.format.extent270 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectBRD4en_US
dc.subjectChromatinen_US
dc.subjectFunctional annotationen_US
dc.subjectGenome-wide association studiesen_US
dc.subjectProstate cancer risken_US
dc.subjectRisk locien_US
dc.subjectSNPsen_US
dc.subjectbreast cancer risken_US
dc.subjectschizophreniaen_US
dc.subjectsuper-enhanceren_US
dc.subjectBinding Sitesen_US
dc.subjectBreast Neoplasmsen_US
dc.subjectChromosome Mappingen_US
dc.subjectComputational Biologyen_US
dc.subjectEnhancer Elements, Geneticen_US
dc.subjectEpigenesis, Geneticen_US
dc.subjectFemaleen_US
dc.subjectGene Expression Regulation, Neoplasticen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectGenome-Wide Association Studyen_US
dc.subjectHistonesen_US
dc.subjectHumansen_US
dc.subjectMaleen_US
dc.subjectNuclear Proteinsen_US
dc.subjectOrgan Specificityen_US
dc.subjectPolymorphism, Single Nucleotideen_US
dc.subjectProstatic Neoplasmsen_US
dc.subjectProtein Bindingen_US
dc.subjectQuantitative Trait Locien_US
dc.subjectReceptors, Androgenen_US
dc.subjectTranscription Factorsen_US
dc.titleBromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer.en_US
dc.typeJournal Article
dcterms.dateAccepted2017-03-11en_US
rioxxterms.versionofrecord10.1186/s12864-017-3620-yen_US
rioxxterms.licenseref.startdate2017-03-31en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfBMC Genomicsen_US
pubs.issue1en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.publication-statusPublished onlineen_US
pubs.volume18en_US
pubs.embargo.termsNot knownen_US
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden_US


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