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dc.contributor.authorWu, Len_US
dc.contributor.authorWang, Jen_US
dc.contributor.authorCai, Qen_US
dc.contributor.authorCavazos, TBen_US
dc.contributor.authorEmami, NCen_US
dc.contributor.authorLong, Jen_US
dc.contributor.authorShu, X-Oen_US
dc.contributor.authorLu, Yen_US
dc.contributor.authorGuo, Xen_US
dc.contributor.authorBauer, JAen_US
dc.contributor.authorPasaniuc, Ben_US
dc.contributor.authorPenney, KLen_US
dc.contributor.authorFreedman, MLen_US
dc.contributor.authorKote-Jarai, Zen_US
dc.contributor.authorWitte, JSen_US
dc.contributor.authorHaiman, CAen_US
dc.contributor.authorEeles, RAen_US
dc.contributor.authorZheng, Wen_US
dc.contributor.authorand the PRACTICAL, CRUK, BPC3, CAPS, PEGASUS Consortiaen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-06-04T10:35:33Z
dc.date.issued2019-07-01en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/31101764en_US
dc.identifier0008-5472.CAN-18-3536en_US
dc.identifier.citationCancer Res, 2019, 79 (13), pp. 3192 - 3204en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3252
dc.identifier.eissn1538-7445en_US
dc.identifier.doi10.1158/0008-5472.CAN-18-3536en_US
dc.description.abstractGenome-wide association study-identified prostate cancer risk variants explain only a relatively small fraction of its familial relative risk, and the genes responsible for many of these identified associations remain unknown. To discover novel prostate cancer genetic loci and possible causal genes at previously identified risk loci, we performed a transcriptome-wide association study in 79,194 cases and 61,112 controls of European ancestry. Using data from the Genotype-Tissue Expression Project, we established genetic models to predict gene expression across the transcriptome for both prostate models and cross-tissue models and evaluated model performance using two independent datasets. We identified significant associations for 137 genes at P < 2.61 × 10-6, a Bonferroni-corrected threshold, including nine genes that remained significant at P < 2.61 × 10-6 after adjusting for all known prostate cancer risk variants in nearby regions. Of the 128 remaining associated genes, 94 have not yet been reported as potential target genes at known loci. We silenced 14 genes and many showed a consistent effect on viability and colony-forming efficiency in three cell lines. Our study provides substantial new information to advance our understanding of prostate cancer genetics and biology. SIGNIFICANCE: This study identifies novel prostate cancer genetic loci and possible causal genes, advancing our understanding of the molecular mechanisms that drive prostate cancer.en_US
dc.format.extent3192 - 3204en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/under-embargo-all-rights-reserveden_US
dc.titleIdentification of Novel Susceptibility Loci and Genes for Prostate Cancer Risk: A Transcriptome-Wide Association Study in Over 140,000 European Descendants.en_US
dc.typeJournal Article
dcterms.dateAccepted2019-05-09en_US
rioxxterms.versionofrecord10.1158/0008-5472.CAN-18-3536en_US
rioxxterms.licenseref.startdate2019-07-01en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfCancer Resen_US
pubs.issue13en_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-statusPublisheden_US
pubs.volume79en_US
pubs.embargo.termsNot knownen_US
icr.researchteamOncogeneticsen_US
dc.contributor.icrauthorEeles, Rosalinden_US
dc.contributor.icrauthorKote-Jarai, Zsofiaen_US


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