Evidence map›Paper›PMID 34035472›Full record

ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2021

Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics.

Max Lam, Chia-Yen Chen, Tian Ge, Yan Xia, David W Hill, Joey W Trampush, Jin Yu, Emma Knowles, Gail Davies, Eli A Stahl and 61 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.1field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Article
  7. Neuronal Actin Remodeling and Its Role in Higher Nervous Activity.International journal of molecular sciences · 2025
    Review
  8. Article
  9. Article
  10. Article
  11. Opportunities for use of neuroimaging in de-risking drug development and improving clinical outcomes in psychiatry: an industry perspective.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

71 authors at 20 institutions in 10 countries.

Max LamDivision of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA.ORCID http://orcid.org/0000-0002-4256-7844
Chia-Yen ChenAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Tian GeStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Yan XiaCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.
David W HillLothian Birth Cohorts, University of Edinburgh, Edinburgh, Scotland, UK.
Joey W TrampushDepartment of Psychiatry and the Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Jin YuDivision of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA.
Emma KnowlesTommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA.
Gail DaviesLothian Birth Cohorts, University of Edinburgh, Edinburgh, Scotland, UK.ORCID http://orcid.org/0000-0003-1120-7026
Eli A StahlRegeneron Pharmaceuticals, Inc., Tarrytown, NY, USA.
Laura HuckinsDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
David C LiewaldLothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0002-0544-7368
Srdjan DjurovicDepartment of Medical Genetics, Oslo University Hospital, Oslo, Norway.
Ingrid MelleDivision of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.ORCID http://orcid.org/0000-0002-9783-548X
Andrea ChristoforouSpaulding Rehabilitation Hospital Boston, Charlestown, MA, USA.
Ivar ReinvangDepartment of Psychology, University of Oslo, Oslo, Norway.
Pamela DeRosseDivision of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA.ORCID http://orcid.org/0000-0003-0823-8163
Astri J LundervoldDepartment of Biological and Medical Psychology, University of Bergen, Bergen, Norway.ORCID http://orcid.org/0000-0002-6819-6164
Vidar M SteenNORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway.
Thomas EspesethDivision of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Katri RäikkönenDepartment of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Elisabeth WidenInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Aarno PalotieInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Johan G ErikssonDepartment of General Practice, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
Ina GieglingDepartment of Psychiatry, Martin Luther University of Halle-Wittenberg, Halle, Germany.
Bettina KonteDepartment of Psychiatry, Martin Luther University of Halle-Wittenberg, Halle, Germany.ORCID http://orcid.org/0000-0001-5287-308X
Annette M HartmannDepartment of Psychiatry, Martin Luther University of Halle-Wittenberg, Halle, Germany.
Panos RoussosDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-4640-6239
Stella GiakoumakiDepartment of Psychology, University of Crete, Crete, Greece.
Katherine E BurdickDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Antony PaytonDivision of Informatics, Imaging & Data Sciences, School of Health Sciences, The University of Manchester, Manchester, UK.
William OllierCentre for Epidemiology, Division of Population Health, Health Services Research & Primary Care, The University of Manchester, Manchester, UK.
Ornit Chiba-FalekDivision of Translational Brain Sciences, Department of Neurology, Bryan Alzheimer's Disease Research Center, and Center for Genomic and Computational Biology, Duke University Medical Center, Durham, NC, USA.ORCID http://orcid.org/0000-0002-2529-8785
Deborah C KoltaiPsychiatry and Behavioral Sciences, Division of Medical Psychology, and Department of Neurology, Duke University Medical Center, Durham, NC, USA.
Anna C NeedWilliam Harvey Research Institute, Queen Mary University of London, London, UK.
Elizabeth T CirulliHelix Inc., San Diego, CA, USA.
Aristotle N VoineskosCampbell Family Mental Health Institute, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.ORCID http://orcid.org/0000-0003-0156-0395
Nikos C Stefanis2nd Department of Psychiatry, National and Kapodistrian University of Athens Medical School, University General Hospital "ATTIKON", Athens, Greece.
Dimitrios AvramopoulosDepartment of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-1492-9104
Alex Hatzimanolis2nd Department of Psychiatry, National and Kapodistrian University of Athens Medical School, University General Hospital "ATTIKON", Athens, Greece.
Nikolaos Smyrnis2nd Department of Psychiatry, National and Kapodistrian University of Athens Medical School, University General Hospital "ATTIKON", Athens, Greece.
Robert M BilderUCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0001-5085-7852
Nelson B FreimerUCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.
Tyrone D CannonDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Edythe LondonUCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-3577-7808
Russell A PoldrackDepartment of Psychology, Stanford University, Palo Alto, CA, USA.ORCID http://orcid.org/0000-0001-6755-0259
Fred W SabbRobert and Beverly Lewis Center for Neuroimaging, University of Oregon, Eugene, OR, USA.
Eliza CongdonUCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.
Emily Drabant Conley23andMe, Inc., Mountain View, CA, USA.
Matthew A ScultWeill Cornell Psychiatry at NewYork-Presbyterian, Weill Cornell Medical Center, New York, NY, USA.
Dwight DickinsonClinical and Translational Neuroscience Branch, Intramural Research Program, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA.
Richard E StraubLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.
Gary DonohoeNeuroimaging, Cognition & Genomics (NICOG) Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland, Galway, Ireland.
Derek MorrisNeuroimaging, Cognition & Genomics (NICOG) Centre, School of Psychology and Discipline of Biochemistry, National University of Ireland, Galway, Ireland.ORCID http://orcid.org/0000-0002-3413-570X
Aiden CorvinNeuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Michael GillNeuropsychiatric Genetics Research Group, Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.ORCID http://orcid.org/0000-0003-0206-5337
Ahmad R HaririLaboratory of NeuroGenetics, Department of Psychology & Neuroscience, Duke University, Durham, NC, USA.
Daniel R WeinbergerLieber Institute for Brain Development, Johns Hopkins University Medical Campus, Baltimore, MD, USA.ORCID http://orcid.org/0000-0003-2409-2969
Neil PendletonDivision of Neuroscience and Experimental Psychology/School of Biological Sciences, Faculty of Biology Medicine and Health, Manchester Academic Health Science Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester, UK.
Panos BitsiosDepartment of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, GR, Greece.
Dan RujescuDepartment of Psychiatry, Martin Luther University of Halle-Wittenberg, Halle, Germany.
Jari LahtiDepartment of Psychology and Logopedics, Faculty of Medicine, University of Helsinki, Helsinki, Finland.ORCID http://orcid.org/0000-0002-4310-5297
Stephanie Le HellardNORMENT, Department of Clinical Science, University of Bergen, Bergen, Norway.
Matthew C KellerInstitute for Behavioral Genetics, University of Colorado, Boulder, CO, USA.
Ole A AndreassenDivision of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.ORCID http://orcid.org/0000-0002-4461-3568
Ian J DearyLothian Birth Cohorts, University of Edinburgh, Edinburgh, Scotland, UK.ORCID http://orcid.org/0000-0002-1733-263X
David C GlahnTommy Fuss Center for Neuropsychiatric Disease Research, Boston Children's Hospital, Boston, MA, USA.
Hailiang HuangStanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Chunyu LiuCenter for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China.ORCID http://orcid.org/0000-0002-5986-4415
Anil K MalhotraDivision of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA.
Todd LenczDivision of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA. tlencz@northwell.edu.ORCID http://orcid.org/0000-0001-8586-338X
University of Helsinki · FIMartin Luther University Halle-Wittenberg · DENHS Lothian · GBOslo University Hospital · NOBroad Institute · USDuke University · USFeinstein Institute for Medical Research · USJohns Hopkins University · USNational and Kapodistrian University of Athens · GRBoston Children's Hospital · USCentral South University · CNHaukeland University Hospital · NOManchester Academic Health Science Centre · GBOllscoil na Gaillimhe – University of Galway · IETrinity College Dublin · IEUniversity of Crete · GR23andMe (United States) · USBiogen (United States) · USBrigham and Women's Hospital · USCentre for Addiction and Mental Health · CA

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
THE FRAMINGHAM HEART STUDYN01HC25195 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI RAMACHANDRAN, VASAN S · 2007 to 2014
$83.8M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
CANDIDATE GENE ASSOCIATION RESOURCE (CARE)N01HC65226 · NHLBI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY · 2007 to 2009
$17.0M
UCLA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR033176 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2011 to 2011
$15.5M
Neurodevelopmental Genomics: Trajectories of Complex PhenotypesRC2MH089983 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GUR, RAQUEL E · 2009 to 2011
$14.3M
Substance Abuse & Behavioral Disinhibition: Integrating Genes & EnvironmentU01DA024417 · NIDA · UNIVERSITY OF MINNESOTA · PI IACONO, WILLIAM G. · 2007 to 2010
$10.8M
2/2 Neurodevelopmental Genomics: Trajectories of Complex PhenotypesRC2MH089924 · NIMH · CHILDREN'S HOSP OF PHILADELPHIA · PI HAKONARSON, HAKON · 2009 to 2011
$10.7M
Quantifying Individual Differences in Midlife Structural Brain Integrity Associated with Later AD/ADRD RiskR01AG049789 · NIA · DUKE UNIVERSITY · PI AHMAD R. HARIRI, TERRIE E MOFFITT · 2015 to 2026
$10.6M
Striatal D2/D3 Dopamine receptor availability in first episode schizophreniaP50MH080173 · NIMH · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI SMITH, GWENN S · 2008 to 2012
$10.4M
Exceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5M
SNP HEALTH ASSOCIATION RESOURCE (SHARE)N02HL64278 · NHLBI · PI CHIN, SIANG · 2007 to 2007
$9.2M
Biotechnology and Biological Sciences Research Council 15/S18386Biotechnology and Biological Sciences Research Council 15/SAG09977Biotechnology and Biological Sciences Research Council BB/F019394/1Chief Scientist Office CZB/4/505Chief Scientist Office CZG/3/2/79Chief Scientist Office CZH/4/213Chief Scientist Office ETM/55CIHRMedical Research Council G0700704Medical Research Council G0700704/84698Medical Research Council MR/K026992/1Medical Research Council MR/T030852/1NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001881NCRR NIH HHS UL1 RR033176NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS N01HC25195NHLBI NIH HHS N01HC55222NHLBI NIH HHS N01HC65226NHLBI NIH HHS N01HC75150NHLBI NIH HHS N01HC85079NHLBI NIH HHS N01HC85080NHLBI NIH HHS N01HC85081NHLBI NIH HHS N01HC85082NHLBI NIH HHS N01HC85083NHLBI NIH HHS N01HC85086NHLBI NIH HHS N02 HL64278NHLBI NIH HHS U01 HL080295NIA NIH HHS K99 AG054573NIA NIH HHS R00 AG054573NIA NIH HHS R01 AG023629NIA NIH HHS R01 AG049789NICHD NIH HHS U54 HD090255NIDA NIH HHS R01 DA033369NIDA NIH HHS RL1 DA024853NIDA NIH HHS U01 DA024417NIDCR NIH HHS UL1 DE019580NIMH NIH HHS K01 MH085812NIMH NIH HHS K01 MH098126NIMH NIH HHS K23 MH077807NIMH NIH HHS P50 MH080173NIMH NIH HHS PL1 MH083271NIMH NIH HHS R01 MH079800NIMH NIH HHS R01 MH080912NIMH NIH HHS R01 MH085018NIMH NIH HHS R01 MH092515NIMH NIH HHS R01 MH110920NIMH NIH HHS R01 MH117646NIMH NIH HHS RC2 MH089924NIMH NIH HHS RC2 MH089983NIMH NIH HHS RL1 MH083269NIMH NIH HHS U01 MH103340NINDS NIH HHS PL1 NS062410
6 · The paper itself

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.

Indexed as

Nootropic AgentsSchizophreniaCognitionGenome-Wide Association StudyHumansTranscriptomeNootropic Agents

Identifiers

PMID34035472
PMCPMC8357785
OpenAlexW3164952088

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.