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dc.contributor.authorBhalala, Oneil G
dc.contributor.authorNath, Artika P
dc.contributor.authorUK Brain Expression Consortium
dc.contributor.authorInouye, Michael
dc.contributor.authorSibley, Christopher R
dc.date.accessioned2018-09-10T22:18:30Z
dc.date.available2018-09-10T22:18:30Z
dc.date.issued2018-08
dc.identifier.issn1553-7390
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/280108
dc.description.abstractSchizophrenia and the affective disorders, here comprising bipolar disorder and major depressive disorder, are psychiatric illnesses that lead to significant morbidity and mortality worldwide. Whilst understanding of their pathobiology remains limited, large case-control studies have recently identified single nucleotide polymorphisms (SNPs) associated with these disorders. However, discerning the functional effects of these SNPs has been difficult as the associated causal genes are unknown. Here we evaluated whether schizophrenia and affective disorder associated-SNPs are correlated with gene expression within human brain tissue. Specifically, to identify expression quantitative trait loci (eQTLs), we leveraged disorder-associated SNPs identified from 11 genome-wide association studies with gene expression levels in post-mortem, neurologically-normal tissue from two independent human brain tissue expression datasets (UK Brain Expression Consortium (UKBEC) and Genotype-Tissue Expression (GTEx)). Utilizing stringent multi-region meta-analyses, we identified 2,224 cis-eQTLs associated with expression of 40 genes, including 11 non-coding RNAs. One cis-eQTL, rs16969968, results in a functionally disruptive missense mutation in CHRNA5, a schizophrenia-implicated gene. Importantly, comparing across tissues, we find that blood eQTLs capture < 10% of brain cis-eQTLs. Contrastingly, > 30% of brain-associated eQTLs are significant in tibial nerve. This study identifies putatively causal genes whose expression in region-specific tissue may contribute to the risk of schizophrenia and affective disorders.
dc.format.mediumElectronic-eCollection
dc.languageeng
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectUK Brain Expression Consortium
dc.subjectBrain
dc.subjectHumans
dc.subjectReceptors, Nicotinic
dc.subjectNerve Tissue Proteins
dc.subjectMood Disorders
dc.subjectSchizophrenia
dc.subjectGene Expression Regulation
dc.subjectGenotype
dc.subjectPolymorphism, Single Nucleotide
dc.subjectQuantitative Trait Loci
dc.subjectPrincipal Component Analysis
dc.subjectGenome-Wide Association Study
dc.titleIdentification of expression quantitative trait loci associated with schizophrenia and affective disorders in normal brain tissue.
dc.typeArticle
prism.issueIdentifier8
prism.publicationDate2018
prism.publicationNamePLoS Genet
prism.startingPagee1007607
prism.volume14
dc.identifier.doi10.17863/CAM.27472
dcterms.dateAccepted2018-08-02
rioxxterms.versionofrecord10.1371/journal.pgen.1007607
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-08-24
dc.contributor.orcidBhalala, Oneil G [0000-0002-4412-7009]
dc.contributor.orcidInouye, Michael [0000-0001-9413-6520]
dc.contributor.orcidSibley, Christopher R [0000-0002-8286-4683]
dc.identifier.eissn1553-7404
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MR/L003120/1)
pubs.funder-project-idBritish Heart Foundation (None)
cam.issuedOnline2018-08-24


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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)