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dc.date.accessioned2020-01-07T19:55:51Z
dc.date.available2020-01-07T19:55:51Z
dc.date.created2019-01-19T11:31:09Z
dc.date.issued2019
dc.identifier.citationSmeland, Olav Bjerkehagen Bahrami, Shahram Frei, Oleksandr Shadrin, Alexey A. O'Connell, Kevin Savage, Jeanne E. Watanabe, Kyoko Krull, Florian Bettella, Francesco Steen, Nils Eiel Ueland, Torill Posthuma, Danielle Djurovic, Srdjan Dale, Anders Andreassen, Ole Andreas . Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence. Molecular Psychiatry. 2019
dc.identifier.urihttp://hdl.handle.net/10852/71955
dc.description.abstractSchizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders associated with cognitive impairment, which is considered a major determinant of functional outcome. Despite this, the etiology of the cognitive impairment is poorly understood, and no satisfactory cognitive treatments exist. Increasing evidence indicates that genetic risk for SCZ may contribute to cognitive impairment, whereas the genetic relationship between BD and cognitive function remains unclear. Here, we combined large genome-wide association study data on SCZ (n = 82,315), BD (n = 51,710), and general intelligence (n = 269,867) to investigate overlap in common genetic variants using conditional false discovery rate (condFDR) analysis. We observed substantial genetic enrichment in both SCZ and BD conditional on associations with intelligence indicating polygenic overlap. Using condFDR analysis, we leveraged this enrichment to increase statistical power and identified 75 distinct genomic loci associated with both SCZ and intelligence, and 12 loci associated with both BD and intelligence at conjunctional FDR < 0.01. Among these loci, 20 are novel for SCZ, and four are novel for BD. Most SCZ risk alleles (61 of 75, 81%) were associated with poorer cognitive performance, whereas most BD risk alleles (9 of 12, 75%) were associated with better cognitive performance. A gene set analysis of the loci shared between SCZ and intelligence implicated biological processes related to neurodevelopment, synaptic integrity, and neurotransmission; the same analysis for BD was underpowered. Altogether, the study demonstrates that both SCZ and BD share genetic influences with intelligence, albeit in a different manner, providing new insights into their genetic architectures.
dc.languageEN
dc.titleGenome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence
dc.typeJournal article
dc.creator.authorSmeland, Olav Bjerkehagen
dc.creator.authorBahrami, Shahram
dc.creator.authorFrei, Oleksandr
dc.creator.authorShadrin, Alexey A.
dc.creator.authorO'Connell, Kevin
dc.creator.authorSavage, Jeanne E.
dc.creator.authorWatanabe, Kyoko
dc.creator.authorKrull, Florian
dc.creator.authorBettella, Francesco
dc.creator.authorSteen, Nils Eiel
dc.creator.authorUeland, Torill
dc.creator.authorPosthuma, Danielle
dc.creator.authorDjurovic, Srdjan
dc.creator.authorDale, Anders
dc.creator.authorAndreassen, Ole Andreas
cristin.unitcode185,53,10,70
cristin.unitnameNORMENT part UiO
cristin.ispublishedtrue
cristin.fulltextpostprint
cristin.qualitycode2
dc.identifier.cristin1660812
dc.identifier.bibliographiccitationinfo:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Molecular Psychiatry&rft.volume=&rft.spage=&rft.date=2019
dc.identifier.jtitleMolecular Psychiatry
dc.identifier.doihttps://doi.org/10.1038/s41380-018-0332-x
dc.identifier.urnURN:NBN:no-75077
dc.type.documentTidsskriftartikkel
dc.type.peerreviewedPeer reviewed
dc.source.issn1359-4184
dc.identifier.fulltextFulltext https://www.duo.uio.no/bitstream/handle/10852/71955/1/Smeland_intelligence_postprint2019.pdf
dc.type.versionAcceptedVersion
dc.relation.projectNFR/248778
dc.relation.projectSKGJ/SKGJ‐MED‐008
dc.relation.projectNFR/248980
dc.relation.projectHSØ/2016–064
dc.relation.projectANDRE/ABCD-USA Consortium (5U2 4DA041123)
dc.relation.projectNFR/249711
dc.relation.projectHSØ/2017-112
dc.relation.projectNFR/262656
dc.relation.projectNFR/223273


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