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dc.contributor.authorZuber, V
dc.contributor.authorBettella, F
dc.contributor.authorWitoelar, A
dc.contributor.authorPRACTICAL Consortium
dc.contributor.authorCRUK GWAS
dc.contributor.authorBCAC Consortium
dc.contributor.authorTRICL Consortium
dc.contributor.authorAndreassen, OA
dc.contributor.authorMills, IG
dc.contributor.authorUrbanucci, A
dc.date.accessioned2019-02-20T12:01:55Z
dc.date.issued2017-03-31
dc.identifier.citationBMC genomics, 2017, 18 (1), pp. 270 - ?
dc.identifier.issn1471-2164
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3078
dc.identifier.eissn1471-2164
dc.identifier.doi10.1186/s12864-017-3620-y
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.
dc.formatElectronic
dc.format.extent270 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectPRACTICAL Consortium
dc.subjectCRUK GWAS
dc.subjectBCAC Consortium
dc.subjectTRICL Consortium
dc.subjectHumans
dc.subjectBreast Neoplasms
dc.subjectProstatic Neoplasms
dc.subjectGenetic Predisposition to Disease
dc.subjectCell Cycle Proteins
dc.subjectNuclear Proteins
dc.subjectHistones
dc.subjectReceptors, Androgen
dc.subjectTranscription Factors
dc.subjectChromosome Mapping
dc.subjectComputational Biology
dc.subjectOrgan Specificity
dc.subjectEpigenesis, Genetic
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectBinding Sites
dc.subjectProtein Binding
dc.subjectPolymorphism, Single Nucleotide
dc.subjectQuantitative Trait Loci
dc.subjectFemale
dc.subjectMale
dc.subjectEnhancer Elements, Genetic
dc.subjectGenome-Wide Association Study
dc.titleBromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer.
dc.typeJournal Article
dcterms.dateAccepted2017-03-11
rioxxterms.versionofrecord10.1186/s12864-017-3620-y
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2017-03-31
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfBMC genomics
pubs.declined2019-02-20T12:01:01.709+0000
pubs.issue1
pubs.notesNot known
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.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
pubs.volume18
pubs.embargo.termsNot known
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden


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