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dc.date.accessioned2018-02-12T11:58:28Z
dc.date.available2018-07-26T22:31:33Z
dc.date.created2017-10-18T23:02:30Z
dc.date.issued2017
dc.identifier.citationSmeland, Olav Bjerkehagen Frei, Oleksandr Kauppi, Karolina Hill, W. David Li, Wen Wang, Yunpeng Krull, Florian Bettella, Francesco Eriksen, Jon Alm Witoelar, Aree Davies, Gail Fan, Chun Chieh Thompson, Wesley Kurt Lam, Max Lencz, Todd Chen, Chi-Hua Ueland, Torill Jönsson, Erik Gunnar Djurovic, Srdjan Deary, Ian J. Dale, Anders Andreassen, Ole Andreas . Identification of genetic loci jointly influencing schizophrenia risk and the cognitive traits of verbal-numerical reasoning, reaction time, and general cognitive function. JAMA psychiatry. 2017, 74(10), 1065-1075
dc.identifier.urihttp://hdl.handle.net/10852/60037
dc.description.abstractImportance: Schizophrenia is associated with widespread cognitive impairments. Although cognitive deficits are one of the factors most strongly associated with functional outcome in schizophrenia, current treatment strategies largely fail to ameliorate these impairments. To develop more efficient treatment strategies in patients with schizophrenia, a better understanding of the pathogenesis of these cognitive deficits is needed. Accumulating evidence indicates that genetic risk of schizophrenia may contribute to cognitive dysfunction. Objective: To identify genomic regions jointly influencing schizophrenia and the cognitive domains of reaction time and verbal-numerical reasoning, as well as general cognitive function, a phenotype that captures the shared variation in performance across cognitive domains. Design, Setting, and Participants: Combining data from genome-wide association studies from multiple phenotypes using conditional false discovery rate analysis provides increased power to discover genetic variants and could elucidate shared molecular genetic mechanisms. Data from the following genome-wide association studies, published from July 24, 2014, to January 17, 2017, were combined: schizophrenia in the Psychiatric Genomics Consortium cohort (n = 79 757 [cases, 34 486; controls, 45 271]); verbal-numerical reasoning (n = 36 035) and reaction time (n = 111 483) in the UK Biobank cohort; and general cognitive function in CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) (n = 53 949) and COGENT (Cognitive Genomics Consortium) (n = 27 888). Main Outcomes and Measures: Genetic loci identified by conditional false discovery rate analysis. Brain messenger RNA expression and brain expression quantitative trait locus functionality were determined. Results: Among the participants in the genome-wide association studies, 21 loci jointly influencing schizophrenia and cognitive traits were identified: 2 loci shared between schizophrenia and verbal-numerical reasoning, 6 loci shared between schizophrenia and reaction time, and 14 loci shared between schizophrenia and general cognitive function. One locus was shared between schizophrenia and 2 cognitive traits and represented the strongest shared signal detected (nearest gene TCF20; chromosome 22q13.2), and was shared between schizophrenia (z score, 5.01; P = 5.53 × 10−7), general cognitive function (z score, –4.43; P = 9.42 × 10−6), and verbal-numerical reasoning (z score, –5.43; P = 5.64 × 10−8). For 18 loci, schizophrenia risk alleles were associated with poorer cognitive performance. The implicated genes are expressed in the developmental and adult human brain. Replicable expression quantitative trait locus functionality was identified for 4 loci in the adult human brain. Conclusions and Relevance: The discovered loci improve the understanding of the common genetic basis underlying schizophrenia and cognitive function, suggesting novel molecular genetic mechanisms.en_US
dc.languageEN
dc.publisherAmerican Medical Association
dc.titleIdentification of genetic loci jointly influencing schizophrenia risk and the cognitive traits of verbal-numerical reasoning, reaction time, and general cognitive functionen_US
dc.typeJournal articleen_US
dc.creator.authorSmeland, Olav Bjerkehagen
dc.creator.authorFrei, Oleksandr
dc.creator.authorKauppi, Karolina
dc.creator.authorHill, W. David
dc.creator.authorLi, Wen
dc.creator.authorWang, Yunpeng
dc.creator.authorKrull, Florian
dc.creator.authorBettella, Francesco
dc.creator.authorEriksen, Jon Alm
dc.creator.authorWitoelar, Aree
dc.creator.authorDavies, Gail
dc.creator.authorFan, Chun Chieh
dc.creator.authorThompson, Wesley Kurt
dc.creator.authorLam, Max
dc.creator.authorLencz, Todd
dc.creator.authorChen, Chi-Hua
dc.creator.authorUeland, Torill
dc.creator.authorJönsson, Erik Gunnar
dc.creator.authorDjurovic, Srdjan
dc.creator.authorDeary, Ian J.
dc.creator.authorDale, Anders
dc.creator.authorAndreassen, Ole Andreas
cristin.unitcode185,53,10,70
cristin.unitnameNORMENT part UiO
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode2
dc.identifier.cristin1505743
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=JAMA psychiatry&rft.volume=74&rft.spage=1065&rft.date=2017
dc.identifier.jtitleJAMA psychiatry
dc.identifier.volume74
dc.identifier.issue10
dc.identifier.startpage1065
dc.identifier.endpage1075
dc.identifier.doihttp://dx.doi.org/10.1001/jamapsychiatry.2017.1986
dc.identifier.urnURN:NBN:no-62699
dc.type.documentTidsskriftartikkelen_US
dc.type.peerreviewedPeer reviewed
dc.source.issn2168-622X
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/60037/4/jamapsychiatry_Smeland_2017_oi_170050.pdf
dc.type.versionPublishedVersion


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