@article{3020239,
    title = "Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics",
    author = "Lam, M. and Chen, C.-Y. and Ge, T. and Xia, Y. and Hill, D.W. and Trampush, J.W. and Yu, J. and Knowles, E. and Davies, G. and Stahl, E.A. and Huckins, L. and Liewald, D.C. and Djurovic, S. and Melle, I. and Christoforou, A. and Reinvang, I. and DeRosse, P. and Lundervold, A.J. and Steen, V.M. and Espeseth, T. and Räikkönen, K. and Widen, E. and Palotie, A. and Eriksson, J.G. and Giegling, I. and Konte, B. and Hartmann, A.M. and Roussos, P. and Giakoumaki, S. and Burdick, K.E. and Payton, A. and Ollier, W. and Chiba-Falek, O. and Koltai, D.C. and Need, A.C. and Cirulli, E.T. and Voineskos, A.N. and Stefanis, N.C. and Avramopoulos, D. and Hatzimanolis, A. and Smyrnis, N. and Bilder, R.M. and Freimer, N.B. and Cannon, T.D. and London, E. and Poldrack, R.A. and Sabb, F.W. and Congdon, E. and Conley, E.D. and Scult, M.A. and Dickinson, D. and Straub, R.E. and Donohoe, G. and Morris, D. and Corvin, A. and Gill, M. and Hariri, A.R. and Weinberger, D.R. and Pendleton, N. and Bitsios, P. and Rujescu, D. and Lahti, J. and Le Hellard, S. and Keller, M.C. and Andreassen, O.A. and Deary, I.J. and Glahn, D.C. and Huang, H. and Liu, C. and Malhotra, A.K. and Lencz, T.",
    journal = "European Neuropsychopharmacology",
    year = "2021",
    volume = "46",
    number = "10",
    pages = "1788-1801",
    publisher = "Springer Nature BV",
    issn = "0924-977X",
    doi = "10.1038/s41386-021-01023-4",
    keywords = "acamprosate;  acetazolamide;  actin binding protein;  almotriptan;  alogliptin;  amantadine;  aminophylline;  amlodipine;  anagliptin;  apremilast;  aripiprazole;  asenapine;  atomoxetine;  atorvastatin;  atovaquone;  benzthiazide;  bortezomib;  brinzolamide;  bromocriptine;  cabergoline;  caffeine;  carfilzomib;  chlortalidone;  clozapine;  coumarin;  dextromethorphan;  diclofenamide;  dihydroergotamine;  dipyridamole;  dopamine;  dorzolamide;  doxofylline;  eletriptan;  ergotamine;  ethoxzolamide;  frovatriptan;  gabapentin;  gabapentin enacarbil;  guanosine triphosphatase;  halothane;  ibudilast;  iloprost;  ketanserin;  ketotifen;  levothyroxine;  linagliptin;  liothyronine;  lisuride;  loxapine;  lubiprostone;  memantine;  methazolamide;  methyclothiazide;  methysergide;  milnacipran;  naratriptan;  nootropic agent;  olanzapine;  oxymetazoline;  pentoxifylline;  piracetam;  pramipexole;  rizatriptan;  roflumilast;  ropinirole;  saxagliptin;  sitagliptin;  sulpiride;  sumatriptan;  tapentadol;  teneligliptin;  tiratricol;  transcriptome;  trelagliptin;  trichlormethiazide;  vildagliptin;  vortioxetine;  yohimbine;  zolmitriptan;  zonisamide;  transcriptome, Article;  autism;  brain tissue;  cheminformatics;  cognition;  controlled study;  drug repositioning;  expression quantitative trait locus;  false positive result;  gene control;  gene identification;  gene linkage disequilibrium;  gene locus;  gene set analysis;  genetic correlation;  genome-wide association study;  human;  large scale production;  Mendelian randomization analysis;  oligodendroglia;  phenotype;  quantitative trait locus mapping;  schizophrenia;  signal transduction;  single nucleotide polymorphism;  transcriptomics;  upregulation;  cognition;  genetics;  genome-wide association study;  schizophrenia, Cognition;  Genome-Wide Association Study;  Humans;  Nootropic Agents;  Schizophrenia;  Transcriptome",
    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. © 2021, The Author(s)."
}