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Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics.
Lam, Max; Chen, Chia-Yen; Ge, Tian; Xia, Yan; Hill, David W; Trampush, Joey W; Yu, Jin; Knowles, Emma; Davies, Gail; Stahl, Eli A; Huckins, Laura; Liewald, David C; Djurovic, Srdjan; Melle, Ingrid; 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; Hartmann, Annette M; Roussos, Panos; Giakoumaki, Stella; Burdick, Katherine E; Payton, Antony; Ollier, William; Chiba-Falek, Ornit; Koltai, Deborah C; Need, Anna C; Cirulli, Elizabeth T; Voineskos, Aristotle N; Stefanis, Nikos C; Avramopoulos, Dimitrios; Hatzimanolis, Alex; Smyrnis, Nikolaos; Bilder, Robert M; Freimer, Nelson B; Cannon, Tyrone D; London, Edythe; Poldrack, Russell A; Sabb, Fred W; Congdon, Eliza; Conley, Emily Drabant; Scult, Matthew A.
Afiliación
  • Lam M; Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA.
  • Chen CY; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Ge T; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Xia Y; Institute for Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
  • Hill DW; Institute of Mental Health, Singapore, Singapore.
  • Trampush JW; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Yu J; Biogen, Inc, Cambridge, MA, USA.
  • Knowles E; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Davies G; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
  • Stahl EA; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
  • Huckins L; Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
  • Liewald DC; Psychiatry Department, SUNY Upstate Medical University, Syracuse, NY, USA.
  • Djurovic S; Lothian Birth Cohorts, University of Edinburgh, Edinburgh, Scotland, UK.
  • Melle I; Lothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, UK.
  • Christoforou A; Department of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
  • Reinvang I; Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA.
  • DeRosse P; Tommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA.
  • Lundervold AJ; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
  • Steen VM; Olin Neuropsychic Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.
  • Espeseth T; Lothian Birth Cohorts, University of Edinburgh, Edinburgh, Scotland, UK.
  • Räikkönen K; Lothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, UK.
  • Widen E; Regeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
  • Palotie A; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Eriksson JG; Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Giegling I; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Konte B; Department of Genetics and Genomic Science and Institute for Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Hartmann AM; Lothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, UK.
  • Roussos P; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.
  • Giakoumaki S; NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Burdick KE; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
  • Payton A; Spaulding Rehabilitation Hospital Boston, Charlestown, MA, USA.
  • Ollier W; Dr. Einar Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
  • Chiba-Falek O; Department of Psychology, University of Oslo, Oslo, Norway.
  • Koltai DC; Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA.
  • Need AC; Institute for Behavioral Science, Feinstein Institutes for Medical Research, Manhasset, NY, USA.
  • Cirulli ET; Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.
  • Voineskos AN; Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway.
  • Stefanis NC; NORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway.
  • Avramopoulos D; Dr. Einar Martens Research Group for Biological Psychiatry, Department of Medical Genetics, Haukeland University Hospital, Bergen, Norway.
  • Hatzimanolis A; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
  • Smyrnis N; Department of Psychology, University of Oslo, Oslo, Norway.
  • Bilder RM; Department of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
  • Freimer NB; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Cannon TD; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • London E; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge, UK.
  • Poldrack RA; Department of Medical Genetics, University of Helsinki and University Central Hospital, Helsinki, Finland.
  • Sabb FW; Department of General Practice, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
  • Congdon E; Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • Conley ED; Folkhälsan Research Center, Helsinki, Finland.
  • Scult MA; Department of Psychiatry, Martin Luther University of Halle-Wittenberg, Halle, Germany.
Neuropsychopharmacology ; 46(10): 1788-1801, 2021 09.
Article en En | MEDLINE | ID: mdl-34035472
ABSTRACT
Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esquizofrenia / Nootrópicos Límite: Humans Idioma: En Revista: Neuropsychopharmacology Asunto de la revista: NEUROLOGIA / PSICOFARMACOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esquizofrenia / Nootrópicos Límite: Humans Idioma: En Revista: Neuropsychopharmacology Asunto de la revista: NEUROLOGIA / PSICOFARMACOLOGIA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos