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Evidence of common genetic overlap between schizophrenia and cognition

Hubbard, Leon, Tansey, Katherine E., Rai, Dheeraj, Jones, Peter, Ripke, Stephan, Chambert, Kimberly D., Moran, Jennifer L., McCarroll, Steven A., Linden, David Edmund Johannes ORCID:, Owen, Michael John ORCID:, O'Donovan, Michael Conlon ORCID:, Walters, James Tynan Rhys ORCID: and Zammit, Stanley ORCID: 2016. Evidence of common genetic overlap between schizophrenia and cognition. Schizophrenia Bulletin 42 (3) , pp. 832-842. 10.1093/schbul/sbv168

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Cognitive impairment is a core feature of schizophrenia but there is limited understanding of the genetic relationship between cognition in the general population and schizophrenia. We examine how common variants associated with schizophrenia en masse contribute to childhood cognitive ability in a population-based sample, and the extent to which common genetic variants associated with childhood cognition explain variation in schizophrenia. Schizophrenia polygenic risk scores were derived from the Psychiatric Genomics Consortium ( n = 69 516) and tested for association with IQ, attention, processing speed, working memory, problem solving, and social cognition in over 5000 children aged 8 from the Avon Longitudinal Study of Parents and Children birth cohort. Polygenic scores for these cognitive domains were tested for association with schizophrenia in a large UK schizophrenia sample ( n = 11 853). Bivariate genome-wide complex trait analysis (GCTA) estimated the amount of shared genetic factors between schizophrenia and cognitive domains. Schizophrenia polygenic risk score was associated with lower performance IQ ( P = .001) and lower full IQ ( P = .013). Polygenic score for performance IQ was associated with increased risk for schizophrenia ( P = 3.56E-04). Bivariate GCTA revealed moderate genetic correlation between schizophrenia and both performance IQ ( rG = −.379, P = 6.62E-05) and full IQ ( rG = −.202, P = 5.00E-03), with approximately 14% of the genetic component of schizophrenia shared with that for performance IQ. Our results support the presence of shared common genetic factors between schizophrenia and childhood cognitive ability. We observe a genetic relationship between schizophrenia and performance IQ but not verbal IQ or other cognitive variables, which may have implications for studies utilizing cognitive endophenotypes for psychosis.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Neuroscience and Mental Health Research Institute (NMHRI)
Advanced Research Computing @ Cardiff (ARCCA)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Subjects: R Medicine > R Medicine (General)
Publisher: Oxford University Press
ISSN: 0586-7614
Funders: MRC
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 1 November 2015
Last Modified: 09 Jul 2023 14:59

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