title: Evidence of Common Genetic Overlap Between Schizophrenia and Cognition.
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 schizophreniaen massecontribute 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.
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK;
authors.forename: Leon
authors.initials: L
authors.lastname: Hubbard
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK;
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Tansey
authors.affiliation: School of Social and Community Medicine, University of Bristol, Bristol, UK;
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Rai
authors.affiliation: Department of Psychiatry, Cambridge University, Cambridge, UK;
authors.forename: Peter
authors.initials: P
authors.lastname: Jones
authors.affiliation: Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA;
authors.forename: Stephan
authors.initials: S
authors.lastname: Ripke
authors.affiliation: Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA;
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Chambert
authors.affiliation: Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA;
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Moran
authors.affiliation: Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA; Department of Genetics, Harvard Medical School, Boston, MA.
authors.forename: Steven A
authors.initials: SA
authors.lastname: McCarroll
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK;
authors.forename: David E J
authors.initials: DE
authors.lastname: Linden
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK;
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK;
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK; WaltersJT@cf.ac.uk.
authors.forename: James T R
authors.initials: JT
authors.lastname: Walters
authors.affiliation: MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK; School of Social and Community Medicine, University of Bristol, Bristol, UK;
authors.forename: Stanley
authors.initials: S
authors.lastname: Zammit
mesh_terms: D000328:Adult; D001288:Attention / Q000502:physiology*; D002648:Child; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007360:Intelligence / Q000502:physiology*; D008297:Male; D020412:Multifactorial Inheritance; D011340:Problem Solving / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology*; D012559:Schizophrenia / Q000503:physiopathology*; D012938:Social Perception; D006113:United Kingdom
keywords: bivariate heritability; cognition; performance IQ; polygenic scoring; schizophrenia