title: Association between polygenic risk for schizophrenia, neurocognition and social cognition across development.
abstract: Breakthroughs in genomics have begun to unravel the genetic architecture of schizophrenia risk, providing methods for quantifying schizophrenia polygenic risk based on common genetic variants. Our objective in the current study was to understand the relationship between schizophrenia genetic risk variants and neurocognitive development in healthy individuals. We first used combined genomic and neurocognitive data from the Philadelphia Neurodevelopmental Cohort (4303 participants ages 8-21 years) to screen 26 neurocognitive phenotypes for their association with schizophrenia polygenic risk. Schizophrenia polygenic risk was estimated for each participant based on summary statistics from the most recent schizophrenia genome-wide association analysis (Psychiatric Genomics Consortium 2014). After correction for multiple comparisons, greater schizophrenia polygenic risk was significantly associated with reduced speed of emotion identification and verbal reasoning. These associations were significant by age 9 years and there was no evidence of interaction between schizophrenia polygenic risk and age on neurocognitive performance. We then looked at the association between schizophrenia polygenic risk and emotion identification speed in the Harvard/MGH Brain Genomics Superstruct Project sample (695 participants ages 18-35 years), where we replicated the association between schizophrenia polygenic risk and emotion identification speed. These analyses provide evidence for a replicable association between polygenic risk for schizophrenia and a specific aspect of social cognition. Our findings indicate that individual differences in genetic risk for schizophrenia are linked with the development of aspects of social cognition and potentially verbal reasoning, and that these associations emerge relatively early in development.
authors.affiliation: Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.|Psychiatry Department, Harvard Medical School, Boston, MA, USA.|Psychology Department, Harvard University, Cambridge, MA, USA.|Broad Institute of MIT and Harvard, Boston, MA, USA.
authors.forename: L
authors.initials: L
authors.lastname: Germine
authors.affiliation: Broad Institute of MIT and Harvard, Boston, MA, USA.|Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Robinson
authors.affiliation: Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.|Psychiatry Department, Harvard Medical School, Boston, MA, USA.|Broad Institute of MIT and Harvard, Boston, MA, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Smoller
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: M E
authors.initials: ME
authors.lastname: Calkins
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Moore
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: Broad Institute of MIT and Harvard, Boston, MA, USA.|Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Daly
authors.affiliation: Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.|Broad Institute of MIT and Harvard, Boston, MA, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Lee
authors.affiliation: Psychology Department, Yale University, New Heaven, CT, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Holmes
authors.affiliation: Psychology Department, Harvard University, Cambridge, MA, USA.|Center for Brain Sciences, Harvard University, Cambridge, MA, USA.|MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Buckner
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Gur
authors.affiliation: Neuropsychiatry Section, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Gur
mesh_terms: D000293:Adolescent; D000367:Age Factors; D016022:Case-Control Studies; D002648:Child; D056348:Emotional Intelligence / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D020412:Multifactorial Inheritance / Q000235:genetics*; D019965:Neurocognitive Disorders / Q000175:diagnosis / Q000235:genetics*; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010641:Phenotype; D011594:Psychometrics; D011930:Reaction Time / Q000235:genetics; D012306:Risk; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012565:Schizophrenic Psychology; D066107:Social Skills; D013223:Statistics as Topic; D055815:Young Adult