title: Independent evidence for an association between general cognitive ability and a genetic locus for educational attainment.
abstract: Cognitive deficits and reduced educational achievement are common in psychiatric illness; understanding the genetic basis of cognitive and educational deficits may be informative about the etiology of psychiatric disorders. A recent, large genome-wide association study (GWAS) reported a genome-wide significant locus for years of education, which subsequently demonstrated association to general cognitive ability ("g") in overlapping cohorts. The current study was designed to test whether GWAS hits for educational attainment are involved in general cognitive ability in an independent, large-scale collection of cohorts. Using cohorts in the Cognitive Genomics Consortium (COGENT; up to 20,495 healthy individuals), we examined the relationship between g and variants associated with educational attainment. We next conducted meta-analyses with 24,189 individuals with neurocognitive data from the educational attainment studies, and then with 53,188 largely independent individuals from a recent GWAS of cognition. A SNP (rs1906252) located at chromosome 6q16.1, previously associated with years of schooling, was significantly associated with g (P = 1.47 × 10(-4) ) in COGENT. The first joint analysis of 43,381 non-overlapping individuals for this a priori-designated locus was strongly significant (P = 4.94 × 10(-7) ), and the second joint analysis of 68,159 non-overlapping individuals was even more robust (P = 1.65 × 10(-9) ). These results provide independent replication, in a large-scale dataset, of a genetic locus associated with cognitive function and education. As sample sizes grow, cognitive GWAS will identify increasing numbers of associated loci, as has been accomplished in other polygenic quantitative traits, which may be relevant to psychiatric illness.
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, New York.|Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York.|Hofstra North Shore - LIJ School of Medicine, Department of Psychiatry, Hempstead, New York.
authors.forename: Joey W
authors.initials: JW
authors.lastname: Trampush
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, New York.|Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York.|Hofstra North Shore - LIJ School of Medicine, Department of Psychiatry, Hempstead, New York.
authors.forename: Todd
authors.initials: T
authors.lastname: Lencz
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Emma
authors.initials: E
authors.lastname: Knowles
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.|Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Gail
authors.initials: G
authors.lastname: Davies
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, New York.
authors.forename: Saurav
authors.initials: S
authors.lastname: Guha
authors.affiliation: Department of Computer Science, Columbia University, New York, New York.|Center for Computational Biology and Bioinformatics, Columbia University, New York, New York.
authors.forename: Itsik
authors.initials: I
authors.lastname: Pe'er
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: David C
authors.initials: DC
authors.lastname: Liewald
authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.|Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: John M
authors.initials: JM
authors.lastname: Starr
authors.affiliation: NorMent, KG Jebsen Centre, Oslo, Norway.|Oslo University Hospital, Oslo, Norway.
authors.forename: Srdjan
authors.initials: S
authors.lastname: Djurovic
authors.affiliation: NorMent, KG Jebsen Centre, Oslo, Norway.|Oslo University Hospital, Oslo, Norway.|University of Oslo, Oslo, Norway.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Melle
authors.affiliation: NorMent, KG Jebsen Centre, Oslo, Norway.|University of Oslo, Oslo, Norway.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Sundet
authors.affiliation: K.G. Jebsen Centre for Psychosis Research, Dr. Einar Martens Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Andrea
authors.initials: A
authors.lastname: Christoforou
authors.affiliation: Department of Psychology, University of Oslo, Oslo, Norway.
authors.forename: Ivar
authors.initials: I
authors.lastname: Reinvang
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, New York.|Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Semanti
authors.initials: S
authors.lastname: Mukherjee
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, New York.|Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Pamela
authors.initials: P
authors.lastname: DeRosse
authors.affiliation: K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Norway.|Department of Biological and Medical Psychology, University of Bergen, Norway.|Kavli Research Centre for Aging and Dementia, Haraldsplass Deaconess Hospital, Bergen, Norway.
authors.forename: Astri
authors.initials: A
authors.lastname: Lundervold
authors.affiliation: K.G. Jebsen Centre for Psychosis Research, Dr. Einar Martens Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Vidar M
authors.initials: VM
authors.lastname: Steen
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, New York.|Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York.
authors.forename: Majnu
authors.initials: M
authors.lastname: John
authors.affiliation: Department of Psychology, University of Oslo, Oslo, Norway.|K.G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
authors.forename: Thomas
authors.initials: T
authors.lastname: Espeseth
authors.affiliation: Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
authors.forename: Katri
authors.initials: K
authors.lastname: Räikkönen
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Widen
authors.affiliation: Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Finland.|Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, United Kingdom.|Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.affiliation: National Institute for Health and Welfare, Finland.|Department of General Practice and Primary Health Care, University of Helsinki, Finland.|Helsinki University Central Hospital, Unit of General Practice, Helsinki, Finland.|Folkhälsan Research Centre, Helsinki, Finland.|Vasa Central Hospital, Vasa, Finland.
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.affiliation: Department of Psychiatry, University of Halle, Halle, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Giegling
authors.affiliation: Department of Psychiatry, University of Halle, Halle, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Konte
authors.affiliation: Department of Psychiatry, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Masashi
authors.initials: M
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authors.affiliation: Department of Psychiatry, The Mount Sinai School of Medicine, New York, New York.
authors.forename: Panos
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authors.affiliation: Department of Psychology, School of Social Sciences, University of Crete, Greece.
authors.forename: Stella
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authors.lastname: Giakoumaki
authors.affiliation: Department of Psychiatry, The Mount Sinai School of Medicine, New York, New York.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Burdick
authors.affiliation: Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, United Kingdom.
authors.forename: Antony
authors.initials: A
authors.lastname: Payton
authors.affiliation: Centre for Integrated Genomic Medical Research, University of Manchester, Manchester, United Kingdom.
authors.forename: William
authors.initials: W
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authors.affiliation: School of Community-Based Medicine, Neurodegeneration Research Group, University of Manchester, Manchester, United Kingdom.
authors.forename: Mike
authors.initials: M
authors.lastname: Horan
authors.affiliation: Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, North Carolina.
authors.forename: Matthew
authors.initials: M
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authors.affiliation: Clinical Brain Disorders Brain and Genes, Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institute of Health, Bethesda, Maryland.
authors.forename: Dwight
authors.initials: D
authors.lastname: Dickinson
authors.affiliation: Clinical Brain Disorders Brain and Genes, Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institute of Health, Bethesda, Maryland.|Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Straub
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Gary
authors.initials: G
authors.lastname: Donohoe
authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Derek
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authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Aiden
authors.initials: A
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authors.affiliation: Neuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Michael
authors.initials: M
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authors.affiliation: Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, North Carolina.
authors.forename: Ahmad
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authors.affiliation: Clinical Brain Disorders Brain and Genes, Cognition and Psychosis Program, Intramural Research Program, National Institute of Mental Health, National Institute of Health, Bethesda, Maryland.|Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, Maryland.
authors.forename: Daniel R
authors.initials: DR
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authors.affiliation: Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, United Kingdom.
authors.forename: Neil
authors.initials: N
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authors.affiliation: Department of Psychiatry, School of Medicine, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Nakao
authors.initials: N
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authors.affiliation: Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
authors.forename: Ariel
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authors.affiliation: Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
authors.forename: Panos
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authors.lastname: Bitsios
authors.affiliation: Department of Psychiatry, University of Halle, Halle, Germany.
authors.forename: Dan
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authors.affiliation: Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.|Institute of Genetics, Folkhälsan Research Centre, Helsinki, Finland.
authors.forename: Jari
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authors.lastname: Lahti
authors.affiliation: K.G. Jebsen Centre for Psychosis Research, Dr. Einar Martens Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Stephanie
authors.initials: S
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authors.affiliation: Institute for Behavioral Genetics, University of Colorado, Boulder, Colorado.
authors.forename: Matthew C
authors.initials: MC
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authors.affiliation: NorMent, KG Jebsen Centre, Oslo, Norway.|Oslo University Hospital, Oslo, Norway.|University of Oslo, Oslo, Norway.
authors.forename: Ole A
authors.initials: OA
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authors.affiliation: Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.|Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
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authors.initials: IJ
authors.lastname: Deary
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: David C
authors.initials: DC
authors.lastname: Glahn
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, New York.|Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York.|Hofstra North Shore - LIJ School of Medicine, Department of Psychiatry, Hempstead, New York.
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mesh_terms: D000328:Adult; D000368:Aged; D003071:Cognition / Q000502:physiology*; D003072:Cognition Disorders / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
keywords: GWAS; educational attainment; general cognitive ability; genetics; neurocognition; proxy phenotype