title: The genetic architecture of pediatric cognitive abilities in the Philadelphia Neurodevelopmental Cohort.
abstract: The objective of this analysis was to examine the genetic architecture of diverse cognitive abilities in children and adolescents, including the magnitude of common genetic effects and patterns of shared and unique genetic influences. Subjects included 3689 members of the Philadelphia Neurodevelopmental Cohort, a general population sample comprising those aged 8-21 years who completed an extensive battery of cognitive tests. We used genome-wide complex trait analysis to estimate the SNP-based heritability of each domain, as well as the genetic correlation between all domains that showed significant genetic influence. Several of the individual domains suggested strong influence of common genetic variants (for example, reading ability, h(2)g=0.43, P=4e-06; emotion identification, h(2)g=0.36, P=1e-05; verbal memory, h(2)g=0.24, P=0.005). The genetic correlations highlighted trait domains that are candidates for joint interrogation in future genetic studies (for example, language reasoning and spatial reasoning, r(g)=0.72, P=0.007). These results can be used to structure future genetic and neuropsychiatric investigations of diverse cognitive abilities.
authors.affiliation: 1] Analytic and Translational Genetics Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA, USA [2] Stanley Center for Psychiatric Research and Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Robinson
authors.affiliation: 1] Analytic and Translational Genetics Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA, USA [2] Stanley Center for Psychiatric Research and Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kirby
authors.affiliation: Department of Psychiatry, Perelman of School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ruparel
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research and Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: L
authors.initials: L
authors.lastname: McGrath
authors.affiliation: 1] Analytic and Translational Genetics Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA, USA [2] Stanley Center for Psychiatric Research and Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA [3] Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland.
authors.forename: V
authors.initials: V
authors.lastname: Anttila
authors.affiliation: 1] Analytic and Translational Genetics Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA, USA [2] Stanley Center for Psychiatric Research and Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: Neale
authors.affiliation: Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: K
authors.initials: K
authors.lastname: Merikangas
authors.affiliation: Office of Genomics Research Coordination, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: Lehner
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: P M A
authors.initials: PM
authors.lastname: Sleiman
authors.affiliation: 1] Analytic and Translational Genetics Unit, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA, USA [2] Stanley Center for Psychiatric Research and Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Daly
authors.affiliation: Department of Psychiatry, Perelman of School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Gur
authors.affiliation: Department of Psychiatry, Perelman of School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Gur
authors.affiliation: Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Hakonarson
mesh_terms: D000293:Adolescent; D002648:Child; D003072:Cognition Disorders / Q000235:genetics*; D015331:Cohort Studies; D018672:Community Health Planning; D002658:Developmental Disabilities / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D023281:Genomics; D005838:Genotype; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D010372:Pediatrics; D010641:Phenotype; D015143:Philadelphia / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D055815:Young Adult