The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia

Alexander L. Richards, Antonio F. Pardinas, Aura Frizzati, Katherine E. Tansey, Amy J. Lynham, Peter Holmans, Sophie E. Legge, Jeanne E. Savage, Ingrid Agartz, Ole A. Andreassen, Gabriella A. M. Blokland, Aiden Corvin, Donna Cosgrove, Franziska Degenhardt, Srdjan Djurovic, Thomas Espeseth, Laura Ferraro, Charlotte Gayer-Anderson, Ina Giegling, Neeltje E. van HarenAnnette M. Hartmann, John J. Hubert, Erik G. Jonsson, Bettina Konte, Leonhard Lennertz, Loes M. Olde Loohuis, Ingrid Melle, Craig Morgan, Derek W. Morris, Robin M. Murray, Hakan Nyman, Roel A. Ophoff, Jim van Os, Tracey L. Petryshen, Diego Quattrone, Marcella Rietschel, Dan Rujescu, Bart P. F. Rutten, Fabian Streit, Jana Strohmaier, Patrick F. Sullivan, Kjetil Sundet, Michael Wagner, Valentina Escott-Price, Michael J. Owen, Gary Donohoe, Michael C. O'Donovan, James T. R. Walters*, GRP Investigators, EUGEI WP2 Group, Schizophrenia Working Group of the Psychiatric Genomics Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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 x 10(-28)) and EA (P = 1.27 x 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.

Original languageEnglish
Pages (from-to)336-344
Number of pages9
JournalSchizophrenia Bulletin
Issue number2
Publication statusPublished - Mar 2020


  • psychiatry
  • genomics
  • intelligence
  • bioinformatics

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