Gene expression imputation across multiple brain regions provides insights into schizophrenia risk

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dc.contributor.authorHuckins, Laura M.en
dc.contributor.authorDobbyn, Amandaen
dc.contributor.authorRuderfer, Douglas M.en
dc.contributor.authorHoffman, Gabrielen
dc.contributor.authorWang, Weiqingen
dc.contributor.authorPardiñas, Antonio F.en
dc.contributor.authorRajagopal, Veera M.en
dc.contributor.authorAls, Thomas D.en
dc.contributor.authorNguyen, Hoang T.en
dc.contributor.authorGirdhar, Kiranen
dc.contributor.authorBoocock, Jamesen
dc.contributor.authorRoussos, Panosen
dc.contributor.authorFromer, Menachemen
dc.contributor.authorKramer, Robinen
dc.contributor.authorDomenici, Enricoen
dc.contributor.authorGamazon, Eric R.en
dc.contributor.authorPurcell, Shaunen
dc.contributor.authorDemontis, Ditteen
dc.contributor.authorBørglum, Anders D.en
dc.contributor.authorWalters, James T. R.en
dc.contributor.authorO’Donovan, Michael C.en
dc.contributor.authorSullivan, Patricken
dc.contributor.authorOwen, Michael J.en
dc.contributor.authorDevlin, Bernieen
dc.contributor.authorSieberts, Solveig K.en
dc.contributor.authorCox, Nancy J.en
dc.contributor.authorKyung Im, Haeen
dc.contributor.authorSklar, Pamelaen
dc.contributor.authorStahl, Eli A.en
dc.contributor.authorDinan, Timothyen
dc.contributor.funderTakeda Pharmaceuticals U.S.A.en
dc.contributor.funderF. Hoffmann-La Rocheen
dc.contributor.funderNational Institutes of Healthen
dc.contributor.funderNational Institute on Agingen
dc.contributor.funderIllinois Department of Public Healthen
dc.contributor.funderTranslational Genomics Research Instituteen
dc.contributor.funderLundbeck Foundationen
dc.contributor.funderStanley Medical Research Instituteen
dc.contributor.funderEuropean Research Councilen
dc.contributor.funderStrategiske Forskningsråden
dc.contributor.funderNovo Nordisk Fondenen
dc.contributor.funderAarhus Universiteten
dc.contributor.funderKøbenhavns Universiteten
dc.date.accessioned2024-05-16T14:45:37Z
dc.date.available2024-05-16T14:45:37Z
dc.date.issued2019-03-25en
dc.description.abstractTranscriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.en
dc.description.sponsorshipNational Institutes of Health (Grants R01MH085542, R01MH093725, P50MH066392, P50MH080405, R01MH097276, RO1-MH-075916, P50M096891, P50MH084053S1, R37MH057881 and R37MH057881S1, HHSN271201300031C, AG02219, AG05138 and MH06692); National Institute on Aging (Grants P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984, U01AG46152); Lundbeck Foundation (Grant no. R102-A9118 and R155-2014-1724); European Research Council (Project no. 294838); ARRA (Awards 1RC2MH089921-01, 1RC2MH090047-01, and 1RC2MH089929-01)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHuckins, L. M., Dobbyn, A., Ruderfer, D. M. et al. (2019) 'Gene expression imputation across multiple brain regions provides insights into schizophrenia risk', Nature Genetics, 51, pp. 659–674. https://doi.org/10.1038/s41588-019-0364-4en
dc.identifier.doihttps://doi.org/10.1038/s41588-019-0364-4en
dc.identifier.eissn1546-1718en
dc.identifier.endpage674en
dc.identifier.issn1061-4036en
dc.identifier.journaltitleNature Geneticsen
dc.identifier.startpage659en
dc.identifier.urihttps://hdl.handle.net/10468/15876
dc.identifier.volume51en
dc.language.isoenen
dc.publisherSpringer Nature Ltd.en
dc.rights© 2019, the Authors, under exclusive licence to Springer Nature America, Inc. This version of the paper has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1038/s41588-019-0364-4en
dc.subjectSchizophreniaen
dc.subjectGene expressionen
dc.subjectMultiple brain regionsen
dc.titleGene expression imputation across multiple brain regions provides insights into schizophrenia risken
dc.typeArticle (peer-reviewed)en
oaire.citation.issue4en
oaire.citation.volume51en
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