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000151594 0247_ $$2doi$$a10.1093/schbul/sbz061
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000151594 041__ $$aEnglish
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000151594 1001_ $$00000-0003-3218-7247$$aRichards, Alexander L$$b0
000151594 245__ $$aThe Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia
000151594 260__ $$aOxford$$bOxford Univ. Press$$c2019
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000151594 520__ $$aBackgroundCognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases.MethodsWe combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases.ResultsPRS for both population IQ (P = 4.39 × 10–28) and EA (P = 1.27 × 10–26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS.ConclusionsCognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.
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000151594 542__ $$2Crossref$$i2019-06-17$$uhttp://creativecommons.org/licenses/by/4.0/
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000151594 650_2 $$2MeSH$$aBipolar Disorder: genetics
000151594 650_2 $$2MeSH$$aDatasets as Topic
000151594 650_2 $$2MeSH$$aDepressive Disorder, Major: genetics
000151594 650_2 $$2MeSH$$aEducational Status
000151594 650_2 $$2MeSH$$aGenome-Wide Association Study
000151594 650_2 $$2MeSH$$aHumans
000151594 650_2 $$2MeSH$$aIntelligence: genetics
000151594 650_2 $$2MeSH$$aMultifactorial Inheritance
000151594 650_2 $$2MeSH$$aPsychotic Disorders: genetics
000151594 650_2 $$2MeSH$$aSchizophrenia: genetics
000151594 7001_ $$aPardiñas, Antonio F$$b1
000151594 7001_ $$aFrizzati, Aura$$b2
000151594 7001_ $$aTansey, Katherine E$$b3
000151594 7001_ $$00000-0002-3189-6888$$aLynham, Amy J$$b4
000151594 7001_ $$aHolmans, Peter$$b5
000151594 7001_ $$aLegge, Sophie E$$b6
000151594 7001_ $$aSavage, Jeanne E$$b7
000151594 7001_ $$aAgartz, Ingrid$$b8
000151594 7001_ $$0P:(DE-HGF)0$$aAndreassen, Ole A$$b9
000151594 7001_ $$aBlokland, Gabriella A M$$b10
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000151594 7001_ $$aCosgrove, Donna$$b12
000151594 7001_ $$aDegenhardt, Franziska$$b13
000151594 7001_ $$aDjurovic, Srdjan$$b14
000151594 7001_ $$aEspeseth, Thomas$$b15
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000151594 7001_ $$aGayer-Anderson, Charlotte$$b17
000151594 7001_ $$aGiegling, Ina$$b18
000151594 7001_ $$avan Haren, Neeltje E$$b19
000151594 7001_ $$aHartmann, Annette M$$b20
000151594 7001_ $$aHubert, John J$$b21
000151594 7001_ $$aJönsson, Erik G$$b22
000151594 7001_ $$aKonte, Bettina$$b23
000151594 7001_ $$aLennertz, Leonhard$$b24
000151594 7001_ $$aOlde Loohuis, Loes M$$b25
000151594 7001_ $$aMelle, Ingrid$$b26
000151594 7001_ $$aMorgan, Craig$$b27
000151594 7001_ $$aMorris, Derek W$$b28
000151594 7001_ $$aMurray, Robin M$$b29
000151594 7001_ $$aNyman, Håkan$$b30
000151594 7001_ $$aOphoff, Roel A$$b31
000151594 7001_ $$avan Os, Jim$$b32
000151594 7001_ $$aPetryshen, Tracey L$$b33
000151594 7001_ $$aQuattrone, Diego$$b34
000151594 7001_ $$aRietschel, Marcella$$b35
000151594 7001_ $$aRujescu, Dan$$b36
000151594 7001_ $$aRutten, Bart P F$$b37
000151594 7001_ $$aStreit, Fabian$$b38
000151594 7001_ $$aStrohmaier, Jana$$b39
000151594 7001_ $$aSullivan, Patrick F$$b40
000151594 7001_ $$aSundet, Kjetil$$b41
000151594 7001_ $$0P:(DE-2719)2000057$$aWagner, Michael$$b42$$udzne
000151594 7001_ $$aEscott-Price, Valentina$$b43
000151594 7001_ $$aOwen, Michael J$$b44
000151594 7001_ $$aDonohoe, Gary$$b45
000151594 7001_ $$aO’Donovan, Michael C$$b46
000151594 7001_ $$0P:(DE-HGF)0$$aWalters, James T R$$b47$$eCorresponding author
000151594 77318 $$2Crossref$$3journal-article$$a10.1093/schbul/sbz061$$b : Oxford University Press (OUP), 2019-06-17$$tSchizophrenia Bulletin$$x0586-7614$$y2019
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000151594 8564_ $$uhttps://academic.oup.com/schizophreniabulletin/article/46/2/336/5519548
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