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Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.
Savage, Jeanne E; Jansen, Philip R; Stringer, Sven; Watanabe, Kyoko; Bryois, Julien; de Leeuw, Christiaan A; Nagel, Mats; Awasthi, Swapnil; Barr, Peter B; Coleman, Jonathan R I; Grasby, Katrina L; Hammerschlag, Anke R; Kaminski, Jakob A; Karlsson, Robert; Krapohl, Eva; Lam, Max; Nygaard, Marianne; Reynolds, Chandra A; Trampush, Joey W; Young, Hannah; Zabaneh, Delilah; Hägg, Sara; Hansell, Narelle K; Karlsson, Ida K; Linnarsson, Sten; Montgomery, Grant W; Muñoz-Manchado, Ana B; Quinlan, Erin B; Schumann, Gunter; Skene, Nathan G; Webb, Bradley T; White, Tonya; Arking, Dan E; Avramopoulos, Dimitrios; Bilder, Robert M; Bitsios, Panos; Burdick, Katherine E; Cannon, Tyrone D; Chiba-Falek, Ornit; Christoforou, Andrea; Cirulli, Elizabeth T; Congdon, Eliza; Corvin, Aiden; Davies, Gail; Deary, Ian J; DeRosse, Pamela; Dickinson, Dwight; Djurovic, Srdjan; Donohoe, Gary; Conley, Emily Drabant.
Afiliação
  • Savage JE; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • Jansen PR; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • Stringer S; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Watanabe K; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • Bryois J; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • de Leeuw CA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Nagel M; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • Awasthi S; Department of Clinical Genetics, Section of Complex Trait Genetics, Neuroscience Campus Amsterdam, VU Medical Center, Amsterdam, The Netherlands.
  • Barr PB; Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
  • Coleman JRI; Department of Psychology, Virginia Commonwealth University, Richmond, VA, USA.
  • Grasby KL; Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
  • Hammerschlag AR; NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Trust, London, UK.
  • Kaminski JA; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • Karlsson R; Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
  • Krapohl E; Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
  • Lam M; Berlin Institute of Health (BIH), Berlin, Germany.
  • Nygaard M; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Reynolds CA; Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
  • Trampush JW; Institute of Mental Health, Singapore, Singapore.
  • Young H; The Danish Twin Registry and the Danish Aging Research Center, Department of Public Health, University of Southern Denmark, Odense, Denmark.
  • Zabaneh D; Epidemiology, Biostatistics, and Biodemography, Department of Public Health, University of Southern Denmark, Odense, Denmark.
  • Hägg S; Department of Psychology, University of California Riverside, Riverside, CA, USA.
  • Hansell NK; BrainWorkup, LLC, Los Angeles, CA, USA.
  • Karlsson IK; Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Linnarsson S; Department of Psychology, University of Minnesota, St. Paul, MN, USA.
  • Montgomery GW; Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK.
  • Muñoz-Manchado AB; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Quinlan EB; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
  • Schumann G; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Skene NG; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Webb BT; QIMR Berghofer Medical Research Institute, Herston, Brisbane, Queensland, Australia.
  • White T; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
  • Arking DE; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Avramopoulos D; Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology, and Neuroscience, MRC-SGDP Centre, King's College London, London, UK.
  • Bilder RM; Centre for Population Neuroscience and Precision Medicine (PONS), Institute of Psychiatry, Psychology, and Neuroscience, MRC-SGDP Centre, King's College London, London, UK.
  • Bitsios P; Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Burdick KE; UCL Institute of Neurology, Queen Square, London, UK.
  • Cannon TD; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA.
  • Chiba-Falek O; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
  • Christoforou A; Department of Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
  • Cirulli ET; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Congdon E; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Corvin A; Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Davies G; UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.
  • Deary IJ; Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, Greece.
  • DeRosse P; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Dickinson D; Mental Illness Research, Education and Clinical Center (VISN 2), James J. Peters VA Medical Center, Bronx, NY, USA.
  • Djurovic S; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Donohoe G; Department of Psychology, Yale University, New Haven, CT, USA.
  • Conley ED; Department of Neurology, Bryan Alzheimer's Disease Research Center, and Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC, USA.
Nat Genet ; 50(7): 912-919, 2018 07.
Article em En | MEDLINE | ID: mdl-29942086
Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inteligência Tipo de estudo: Clinical_trials / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adolescent / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Inteligência Tipo de estudo: Clinical_trials / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limite: Adolescent / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2018 Tipo de documento: Article