Evidence of common genetic overlap between schizophrenia and cognition

Leon Hubbard, Katherine E. Tansey, Dheeraj Rai, Peter Jones, Stephan Ripke, Kimberly D. Chambert, Jennifer L. Moran, Steven A. McCarroll, David Edmund Johannes Linden, Michael John Owen, Michael Conlon O'Donovan, James Tynan Rhys Walters, Stanley Zammit

Research output: Contribution to journalArticle (Academic Journal)peer-review

57 Citations (Scopus)
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Abstract

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 (r G = −.379, P = 6.62E-05) and full IQ (r G = −.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.
Original languageEnglish
Pages (from-to)832-842
Number of pages11
JournalSchizophrenia Bulletin
Volume42
Issue number3
Early online date16 Dec 2015
DOIs
Publication statusPublished - May 2016

Keywords

  • schizophrenia
  • cognition
  • performance IQ
  • polygenic scoring
  • bivariate heritability

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