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Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets.
Lam, Max; Trampush, Joey W; Yu, Jin; Knowles, Emma; Davies, Gail; Liewald, David C; Starr, John M; Djurovic, Srdjan; Melle, Ingrid; Sundet, Kjetil; Christoforou, Andrea; Reinvang, Ivar; DeRosse, Pamela; Lundervold, Astri J; Steen, Vidar M; Espeseth, Thomas; Räikkönen, Katri; Widen, Elisabeth; Palotie, Aarno; Eriksson, Johan G; Giegling, Ina; Konte, Bettina; Roussos, Panos; Giakoumaki, Stella; Burdick, Katherine E; Payton, Antony; Ollier, William; Chiba-Falek, Ornit; Attix, Deborah K; Need, Anna C; Cirulli, Elizabeth T; Voineskos, Aristotle N; Stefanis, Nikos C; Avramopoulos, Dimitrios; Hatzimanolis, Alex; Arking, Dan E; Smyrnis, Nikolaos; Bilder, Robert M; Freimer, Nelson A; Cannon, Tyrone D; London, Edythe; Poldrack, Russell A; Sabb, Fred W; Congdon, Eliza; Conley, Emily Drabant; Scult, Matthew A; Dickinson, Dwight; Straub, Richard E; Donohoe, Gary; Morris, Derek.
Afiliação
  • Lam M; Institute of Mental Health, Singapore, Singapore.
  • Trampush JW; BrainWorkup, LLC, Los Angeles, CA, USA.
  • Yu J; Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.
  • Knowles E; Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
  • Davies G; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Department of Psychology, University of Edinburgh, Edinburgh, UK.
  • Liewald DC; Department of Psychology, University of Edinburgh, Edinburgh, UK.
  • Starr JM; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK; Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
  • Djurovic S; Department of Medical Genetics, Oslo University Hospital, University of Bergen, Oslo, Norway; NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen, Bergen, Norway.
  • Melle I; NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen, Bergen, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
  • Sundet K; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
  • Christoforou A; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
  • Reinvang I; Department of Psychology, University of Oslo, Oslo, Norway.
  • DeRosse P; Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.
  • Lundervold AJ; Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
  • Steen VM; NORMENT, K.G. Jebsen Centre for Psychosis Research, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
  • Espeseth T; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.
  • Räikkönen K; Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland.
  • Widen E; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Palotie A; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK; Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.
  • Eriksson JG; Department of General Practice, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; National Institute for Health and Welfare, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland.
  • Giegling I; Department of Psychiatry, Martin Luther University of Halle-Wittenberg, Halle, Germany.
  • Konte B; Department of Psychiatry, Martin Luther University of Halle-Wittenberg, Halle, Germany.
  • Roussos P; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Mental Illness Research, Education, and Clinical Center (VISN 2), James J
  • Giakoumaki S; Department of Psychology, University of Crete, Crete, Greece.
  • Burdick KE; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Mental Illness Research, Education, and Clinical Center (VISN 2), James J. Peters VA Medical Center, Bronx, NY, USA; Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Payton A; Centre for Epidemiology, Division of Population Health, Health Services Research & Primary Care, The University of Manchester, Manchester, UK.
  • Ollier W; Centre for Epidemiology, Division of Population Health, Health Services Research & Primary Care, The University of Manchester, Manchester, UK; Centre for Integrated Genomic Medical Research, Institute of Population Health, University of Manchester, Manchester, UK.
  • Chiba-Falek O; Department of Neurology, Bryan Alzheimer's Disease Research Center and Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC, USA.
  • Attix DK; Department of Neurology, Bryan Alzheimer's Disease Research Center and Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC, USA; Department of Psychiatry and Behavioral Sciences, Division of Medical Psychology, Duke University Medical Center, Durham, NC, USA.
  • Need AC; Division of Brain Sciences, Department of Medicine, Imperial College, London, UK.
  • Cirulli ET; Human Longevity Inc., Durham, NC, USA.
  • Voineskos AN; Campbell Family Mental Health Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, Canada.
  • Stefanis NC; Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, Athens, Greece; University Mental Health Research Institute, Athens, Greece; Neurobiology Research Institute, Theodor-Theohari Cozzika Foundation, Athens, Greece.
  • Avramopoulos D; Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Hatzimanolis A; Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, Athens, Greece; University Mental Health Research Institute, Athens, Greece; Neurobiology Research Institute, Theodor-Theohari Cozzika Foundation, Athens, Greece.
  • Arking DE; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Smyrnis N; Department of Psychiatry, National and Kapodistrian University of Athens Medical School, Eginition Hospital, Athens, Greece; University Mental Health Research Institute, Athens, Greece.
  • Bilder RM; UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.
  • Freimer NA; UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.
  • Cannon TD; Department of Psychology, Yale University, New Haven, CT, USA.
  • London E; UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.
  • Poldrack RA; Department of Psychology, Stanford University, Palo Alto, CA, USA.
  • Sabb FW; Robert and Beverly Lewis Center for Neuroimaging, University of Oregon, Eugene, OR, USA.
  • Congdon E; UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.
  • Conley ED; 23andMe, Inc., Mountain View, CA, USA.
  • Scult MA; Laboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA.
  • Dickinson D; Clinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA.
  • Straub RE; Lieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
  • Donohoe G; Neuroimaging, Cognition & Genomics (NICOG) Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland, Galway, Ireland.
  • Morris D; Neuroimaging, Cognition & Genomics (NICOG) Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland, Galway, Ireland.
Cell Rep ; 21(9): 2597-2613, 2017 Nov 28.
Article em En | MEDLINE | ID: mdl-29186694
Here, we present a large (n = 107,207) genome-wide association study (GWAS) of general cognitive ability ("g"), further enhanced by combining results with a large-scale GWAS of educational attainment. We identified 70 independent genomic loci associated with general cognitive ability. Results showed significant enrichment for genes causing Mendelian disorders with an intellectual disability phenotype. Competitive pathway analysis implicated the biological processes of neurogenesis and synaptic regulation, as well as the gene targets of two pharmacologic agents: cinnarizine, a T-type calcium channel blocker, and LY97241, a potassium channel inhibitor. Transcriptome-wide and epigenome-wide analysis revealed that the implicated loci were enriched for genes expressed across all brain regions (most strongly in the cerebellum). Enrichment was exclusive to genes expressed in neurons but not oligodendrocytes or astrocytes. Finally, we report genetic correlations between cognitive ability and disparate phenotypes including psychiatric disorders, several autoimmune disorders, longevity, and maternal age at first birth.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nootrópicos / Estudo de Associação Genômica Ampla Tipo de estudo: Systematic_reviews Limite: Female / Humans / Male Idioma: En Revista: Cell Rep Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Singapura
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Nootrópicos / Estudo de Associação Genômica Ampla Tipo de estudo: Systematic_reviews Limite: Female / Humans / Male Idioma: En Revista: Cell Rep Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Singapura