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dc.contributor.authorGuo, Huien
dc.contributor.authorFortune, Maryen
dc.contributor.authorBurren, Oliveren
dc.contributor.authorSchofield, Ellenen
dc.contributor.authorTodd, Johnen
dc.contributor.authorWallace, Catrionaen
dc.date.accessioned2015-05-14T13:57:51Z
dc.date.available2015-05-14T13:57:51Z
dc.date.issued2015-03-05en
dc.identifier.citationHuman Molecular Genetics (2015) 24 (12): 3305-3313. DOI: 10.1093/hmg/ddv077en
dc.identifier.issn0964-6906
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/247700
dc.description.abstractThe genes and cells that mediate genetic associations identified through genome-wide association studies (GWAS) are only partially understood. Several studies that have investigated the genetic regulation of gene expression have shown that disease-associated variants are over-represented amongst expression quantitative trait loci (eQTL) variants. Evidence for colocalisation of eQTL and disease causal variants can suggest causal genes and cells for these genetic associations. Here, we used colocalisation analysis to investigate whether 595 genetic associations to ten immune-mediated diseases are consistent with a causal variant that regulates, in cis, gene expression in resting B cells, and in resting and stimulated monocytes. Previously published candidate causal genes were over-represented amongst genes exhibiting colocalisation (odds ratio > 1.5), and we identified evidence for colocalisation (posterior odds > 5) between cis eQTLs in at least one cell type and at least one disease for six genes: ADAM15, RGS1, CARD9, LTBR, CTSH and SYNGR1. We identified cell-specific effects, such as for CTSH, the expression of which in monocytes, but not in B cells, may mediate type 1 diabetes and narcolepsy associations in the chromosome 15q25.1 region. Our results demonstrate the utility of integrating genetic studies of disease and gene expression for highlighting causal genes and cell types.
dc.description.sponsorshipThis work was supported by the JDRF [9-2011-253], the Wellcome Trust [091157] and the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. The research leading to these results has received funding from the European Union′s 7th Framework Programme (FP7/2007-2013) under grant agreement no.241447 (NAIMIT). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award [100140]. The Wellcome Trust funded C.W. and H.G. [089989] and M.D.F. [099772]. ImmunoBase.org is supported by Eli Lilly and Company. Funding to pay the Open Access publication charges for this article was provided by the Wellcome Trust.
dc.languageEnglishen
dc.language.isoenen
dc.publisherOxford University Press
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.titleIntegration of disease association and eQTL data using a Bayesian colocalisation approach highlights six candidate causal genes in immune-mediated diseasesen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/hmg/ddv077en
prism.endingPage3313
prism.publicationDate2015en
prism.publicationNameHuman Molecular Geneticsen
prism.startingPage3305
prism.volume24en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderNIHR
dc.rioxxterms.projectid091157
dc.rioxxterms.projectid100140
dc.rioxxterms.projectid089989
dc.rioxxterms.projectid099772
dcterms.dateAccepted2015-02-24en
rioxxterms.versionofrecord10.1093/hmg/ddv077en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-03-05en
dc.contributor.orcidFortune, Mary [0000-0002-6006-4343]
dc.contributor.orcidBurren, Oliver [0000-0002-3388-5760]
dc.contributor.orcidWallace, Catriona [0000-0001-9755-1703]
dc.identifier.eissn1460-2083
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (089989/Z/09/Z)
pubs.funder-project-idWellcome Trust (100140/Z/12/Z)
pubs.funder-project-idEC FP7 CP (241447)
pubs.funder-project-idWellcome Trust (099772/Z/12/Z)
pubs.funder-project-idWellcome Trust (091157/Z/10/B)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales