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dc.contributor.authorMoradi Marjaneh, Mahdi
dc.contributor.authorBeesley, Jonathan
dc.contributor.authorO’Mara, Tracy A.
dc.contributor.authorMukhopadhyay, Pamela
dc.contributor.authorKoufariotis, Lambros T.
dc.contributor.authorKazakoff, Stephen
dc.contributor.authorHussein, Nehal
dc.contributor.authorFachal, Laura
dc.contributor.authorBartonicek, Nenad
dc.contributor.authorHillman, Kristine M.
dc.contributor.authorKaufmann, Susanne
dc.contributor.authorSivakumaran, Haran
dc.contributor.authorSmart, Chanel E.
dc.contributor.authorMcCart Reed, Amy E.
dc.contributor.authorFerguson, Kaltin
dc.contributor.authorSaunus, Jodi M.
dc.contributor.authorLakhani, Sunil R.
dc.contributor.authorBarnes, Daniel R.
dc.contributor.authorAntoniou, Antonis C.
dc.contributor.authorDinger, Marcel E.
dc.contributor.authorWaddell, Nicola
dc.contributor.authorEaston, Douglas F.
dc.contributor.authorDunning, Alison M.
dc.contributor.authorChenevix-Trench, Georgia
dc.contributor.authorEdwards, Stacey L.
dc.contributor.authorFrench, Juliet D.
dc.date.accessioned2021-01-06T16:13:39Z
dc.date.available2021-01-06T16:13:39Z
dc.date.issued2020-01-07
dc.date.submitted2019-01-14
dc.identifier.others13059-019-1876-z
dc.identifier.other1876
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/315781
dc.descriptionFunder: National Breast Cancer Foundation; doi: http://dx.doi.org/10.13039/501100001026
dc.description.abstractAbstract: Background: Genetic variants identified through genome-wide association studies (GWAS) are predominantly non-coding and typically attributed to altered regulatory elements such as enhancers and promoters. However, the contribution of non-coding RNAs to complex traits is not clear. Results: Using targeted RNA sequencing, we systematically annotated multi-exonic non-coding RNA (mencRNA) genes transcribed from 1.5-Mb intervals surrounding 139 breast cancer GWAS signals and assessed their contribution to breast cancer risk. We identify more than 4000 mencRNA genes and show their expression distinguishes normal breast tissue from tumors and different breast cancer subtypes. Importantly, breast cancer risk variants, identified through genetic fine-mapping, are significantly enriched in mencRNA exons, but not the promoters or introns. eQTL analyses identify mencRNAs whose expression is associated with risk variants. Furthermore, chromatin interaction data identify hundreds of mencRNA promoters that loop to regions that contain breast cancer risk variants. Conclusions: We have compiled the largest catalog of breast cancer-associated mencRNAs to date and provide evidence that modulation of mencRNAs by GWAS variants may provide an alternative mechanism underlying complex traits.
dc.languageen
dc.publisherBioMed Central
dc.rightsAttribution 4.0 International (CC BY 4.0)en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectResearch
dc.titleNon-coding RNAs underlie genetic predisposition to breast cancer
dc.typeArticle
dc.date.updated2021-01-06T16:13:38Z
prism.issueIdentifier1
prism.publicationNameGenome Biology
prism.volume21
dc.identifier.doi10.17863/CAM.62894
dcterms.dateAccepted2019-11-01
rioxxterms.versionofrecord10.1186/s13059-019-1876-z
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidFrench, Juliet D. [0000-0002-9770-0198]
dc.identifier.eissn1474-760X
pubs.funder-project-idNational Health and Medical Research Council (APP1058421, 1135932, 1117073, 1139071, 1111246)
pubs.funder-project-idHorizon 2020 (MSCA-IF-2014-EF-656144)


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