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Ripke, Stephan
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article
Evidence of common genetic overlap between schizophrenia and cognition
Abstract
Cognitive impairment is a core feature of schizophrenia but there islimited understanding of the genetic relationship betweencognition in the general population andschizophrenia. We examine how common variants associated withschizophrenia <em>en masse</em> contribute to childhood cognitiveability in a population-based sample, and the extent to which commongenetic variants associatedwith childhood cognition explain variation inschizophrenia. Schizophrenia polygenic risk scores were derived from thePsychiatricGenomics Consortium (<em>n</em> = 69 516) andtested for association with IQ, attention, processing speed, workingmemory, problem solving, and social cognitionin over 5000 children aged 8 from the AvonLongitudinal Study of Parents and Children birth cohort. Polygenicscores for thesecognitive domains were tested for association withschizophrenia in a large UK schizophrenia sample (<em>n</em> = 11 853).Bivariate genome-wide complex trait analysis (GCTA) estimated the amountof shared genetic factors between schizophreniaand cognitive domains. Schizophrenia polygenic riskscore was associated with lower performance IQ (<em>P</em> = .001) and lower full IQ (<em>P</em> = .013). Polygenic score for performance IQ was associated with increased risk for schizophrenia (<em>P</em> = 3.56E-04). Bivariate GCTA revealed moderate genetic correlation between schizophrenia and both performance IQ (<em>r</em><sub>G</sub> = −.379, <em>P</em> = 6.62E-05) and full IQ (<em>r</em><sub>G</sub> = −.202, <em>P</em> = 5.00E-03), withapproximately 14% of the genetic component of schizophrenia shared withthat for performance IQ. Our resultssupport the presence of shared common geneticfactors between schizophrenia and childhood cognitive ability. Weobserve agenetic relationship between schizophrenia andperformance IQ but not verbal IQ or other cognitive variables, which mayhaveimplications for studies utilizing cognitiveendophenotypes for psychosis.