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dc.contributor.authorDadaev, T.
dc.contributor.authorSaunders, E.J.
dc.contributor.authorNewcombe, P.J.
dc.date.accessioned2019-06-21T18:46:35Z
dc.date.available2019-06-21T18:46:35Z
dc.date.issued2018
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85048420948&doi=10.1038%2fs41467-018-04109-8&partnerID=40&md5=575cc99635f00ccb89df4128325ecf20
dc.identifier.urihttp://hdl.handle.net/10713/9804
dc.description.abstractProstate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. Copyright 2018 The Author(s).en_US
dc.description.urihttps://dx.doi.org/10.1038/s41467-018-04109-8en_US
dc.language.isoen-USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofNature Communications
dc.subjectAfrican Continental Ancestry Groupen_US
dc.subjectAlgorithmsen_US
dc.subjectBayes Theoremen_US
dc.subjectChromosome Mappingen_US
dc.subjectEuropean Continental Ancestry Groupen_US
dc.subjectGenetic Predisposition to Diseaseen_US
dc.subjectGenome-Wide Association Studyen_US
dc.subjectHumansen_US
dc.subjectMaleen_US
dc.subjectMolecular Sequence Annotationen_US
dc.subjectprostate canceren_US
dc.titleFine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variantsen_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41467-018-04109-8
dc.identifier.pmid29892050


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