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RESEARCH PRODUCT
The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia
Laura FerraroMichael John OwenTracey L. PetryshenTracey L. PetryshenFranziska DegenhardtDerek W. MorrisAlexander RichardsAura FrizzatiIngrid AgartzIngrid AgartzLeonhard LennertzIngrid MelleFabian StreitJim Van OsJim Van OsJim Van OsBart P. F. RuttenBettina KonteValentina Escott-priceAnnette M. HartmannHåkan NymanOle A. AndreassenJana StrohmaierDiego QuattroneJohn HubertGary DonohoeSophie E. LeggeRoel A. OphoffRoel A. OphoffLoes M. Olde LoohuisAmy LynhamDan RujescuGabriëlla A.m. BloklandJames T.r. WaltersJeanne E. SavagePeter HolmansCraig MorganErik G. JönssonErik G. JönssonRobin M. MurrayNeeltje E.m. Van HarenNeeltje E.m. Van HarenKjetil SundetCharlotte Gayer-andersonAntonio F. PardiñasDonna CosgroveMichael WagnerMichael WagnerMarcella RietschelMichael Conlon O'donovanAiden CorvinPatrick F. SullivanThomas EspesethIna GieglingKatherine E. TanseySrdjan Djurovicsubject
Multifactorial InheritanceBipolar DisorderDatasets as TopicINTELLIGENCEGenome-wide association study0302 clinical medicinegenetics [Schizophrenia]education.field_of_studyHERITABILITYCOMMON VARIANTSCognitionbioinformaticsintelligencepsychiatryABILITYPsychiatry and Mental healthSchizophreniaMajor depressive disorderEducational Statuspsychiatry genomics intelligence bioinformaticsClinical psychologyPopulationgenetics [Psychotic Disorders]behavioral disciplines and activities03 medical and health sciencesmental disordersgenomicsmedicineHumansBipolar disorderddc:610GENOME-WIDE ASSOCIATIONeducationSettore MED/25 - PsichiatriaMETAANALYSISGenetic associationDepressive Disorder MajorENDOPHENOTYPESbusiness.industryMEMORYCONSORTIUMgenetics [Depressive Disorder Major]PERFORMANCEmedicine.disease030227 psychiatryPsychotic Disordersgenetics [Intelligence]EndophenotypeSchizophreniabusiness030217 neurology & neurosurgerygenetics [Bipolar Disorder]Regular ArticlesGenome-Wide Association Studydescription
Abstract Background Cognitive 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. Methods We 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. Results PRS 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. Conclusions Cognition 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2020-02-26 |