The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia

Richards, Alexander L and Pardiñas, Antonio F and Frizzati, Aura and Tansey, Katherine E and Lynham, Amy J and Holmans, Peter and Legge, Sophie E and Savage, Jeanne E and Agartz, Ingrid and Andreassen, Ole A and Blokland, Gabriella A M and Corvin, Aiden and Cosgrove, Donna and Degenhardt, Franziska and Djurovic, Srdjan and Espeseth, Thomas and Ferraro, Laura and Gayer-Anderson, Charlotte and Giegling, Ina and van Haren, Neeltje E and Hartmann, Annette M and Hubert, John J and Jönsson, Erik G and Konte, Bettina and Lennertz, Leonhard and Olde Loohuis, Loes M and Melle, Ingrid and Morgan, Craig and Morris, Derek W and Murray, Robin M and Nyman, Håkan and Ophoff, Roel A and van Os, Jim and Petryshen, Tracey L and Quattrone, Diego and Rietschel, Marcella and Rujescu, Dan and Rutten, Bart P F and Streit, Fabian and Strohmaier, Jana and Sullivan, Patrick F and Sundet, Kjetil and Wagner, Michael and Escott-Price, Valentina and Owen, Michael J and Donohoe, Gary and O'Donovan, Michael C and Walters, James T R and Knight, Jo (2020) The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia. Schizophrenia Bulletin, 46 (2). pp. 336-344. ISSN 0586-7614

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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.

Item Type:
Journal Article
Journal or Publication Title:
Schizophrenia Bulletin
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© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.
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Deposited On:
16 Aug 2019 10:25
Last Modified:
23 Sep 2020 05:31