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

Publication ,  Journal Article
Lam, M; Chen, C-Y; Ge, T; Xia, Y; Hill, DW; Trampush, JW; Yu, J; Knowles, E; Davies, G; Stahl, EA; Huckins, L; Liewald, DC; Djurovic, S ...
Published in: Neuropsychopharmacology
September 2021

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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Published In

Neuropsychopharmacology

DOI

EISSN

1740-634X

Publication Date

September 2021

Volume

46

Issue

10

Start / End Page

1788 / 1801

Location

England

Related Subject Headings

  • Transcriptome
  • Schizophrenia
  • Psychiatry
  • Nootropic Agents
  • Humans
  • Genome-Wide Association Study
  • Cognition
  • 5202 Biological psychology
  • 3209 Neurosciences
  • 17 Psychology and Cognitive Sciences
 

Citation

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ICMJE
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Lam, M., Chen, C.-Y., Ge, T., Xia, Y., Hill, D. W., Trampush, J. W., … Lencz, T. (2021). Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics. Neuropsychopharmacology, 46(10), 1788–1801. https://doi.org/10.1038/s41386-021-01023-4
Lam, Max, Chia-Yen Chen, Tian Ge, Yan Xia, David W. Hill, Joey W. Trampush, Jin Yu, et al. “Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics.Neuropsychopharmacology 46, no. 10 (September 2021): 1788–1801. https://doi.org/10.1038/s41386-021-01023-4.
Lam M, Chen C-Y, Ge T, Xia Y, Hill DW, Trampush JW, et al. Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics. Neuropsychopharmacology. 2021 Sep;46(10):1788–801.
Lam, Max, et al. “Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics.Neuropsychopharmacology, vol. 46, no. 10, Sept. 2021, pp. 1788–801. Pubmed, doi:10.1038/s41386-021-01023-4.
Lam M, Chen C-Y, Ge T, Xia Y, Hill DW, Trampush JW, Yu J, Knowles E, Davies G, Stahl EA, Huckins L, Liewald DC, Djurovic S, Melle I, Christoforou A, Reinvang I, DeRosse P, Lundervold AJ, Steen VM, Espeseth T, Räikkönen K, Widen E, Palotie A, Eriksson JG, Giegling I, Konte B, Hartmann AM, Roussos P, Giakoumaki S, Burdick KE, Payton A, Ollier W, Chiba-Falek O, Koltai DC, Need AC, Cirulli ET, Voineskos AN, Stefanis NC, Avramopoulos D, Hatzimanolis A, Smyrnis N, Bilder RM, Freimer NB, Cannon TD, London E, Poldrack RA, Sabb FW, Congdon E, Conley ED, Scult MA, Dickinson D, Straub RE, Donohoe G, Morris D, Corvin A, Gill M, Hariri AR, Weinberger DR, Pendleton N, Bitsios P, Rujescu D, Lahti J, Le Hellard S, Keller MC, Andreassen OA, Deary IJ, Glahn DC, Huang H, Liu C, Malhotra AK, Lencz T. Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics. Neuropsychopharmacology. 2021 Sep;46(10):1788–1801.

Published In

Neuropsychopharmacology

DOI

EISSN

1740-634X

Publication Date

September 2021

Volume

46

Issue

10

Start / End Page

1788 / 1801

Location

England

Related Subject Headings

  • Transcriptome
  • Schizophrenia
  • Psychiatry
  • Nootropic Agents
  • Humans
  • Genome-Wide Association Study
  • Cognition
  • 5202 Biological psychology
  • 3209 Neurosciences
  • 17 Psychology and Cognitive Sciences