TY - JOUR
TI - Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics
AU - Lam, M.
AU - Chen, C.-Y.
AU - Ge, T.
AU - Xia, Y.
AU - Hill, D.W.
AU - Trampush, J.W.
AU - Yu, J.
AU - Knowles, E.
AU - Davies, G.
AU - Stahl, E.A.
AU - Huckins, L.
AU - Liewald, D.C.
AU - Djurovic, S.
AU - Melle, I.
AU - Christoforou, A.
AU - Reinvang, I.
AU - DeRosse, P.
AU - Lundervold, A.J.
AU - Steen, V.M.
AU - Espeseth, T.
AU - Räikkönen, K.
AU - Widen, E.
AU - Palotie, A.
AU - Eriksson, J.G.
AU - Giegling, I.
AU - Konte, B.
AU - Hartmann, A.M.
AU - Roussos, P.
AU - Giakoumaki, S.
AU - Burdick, K.E.
AU - Payton, A.
AU - Ollier, W.
AU - Chiba-Falek, O.
AU - Koltai, D.C.
AU - Need, A.C.
AU - Cirulli, E.T.
AU - Voineskos, A.N.
AU - Stefanis, N.C.
AU - Avramopoulos, D.
AU - Hatzimanolis, A.
AU - Smyrnis, N.
AU - Bilder, R.M.
AU - Freimer, N.B.
AU - Cannon, T.D.
AU - London, E.
AU - Poldrack, R.A.
AU - Sabb, F.W.
AU - Congdon, E.
AU - Conley, E.D.
AU - Scult, M.A.
AU - Dickinson, D.
AU - Straub, R.E.
AU - Donohoe, G.
AU - Morris, D.
AU - Corvin, A.
AU - Gill, M.
AU - Hariri, A.R.
AU - Weinberger, D.R.
AU - Pendleton, N.
AU - Bitsios, P.
AU - Rujescu, D.
AU - Lahti, J.
AU - Le Hellard, S.
AU - Keller, M.C.
AU - Andreassen, O.A.
AU - Deary, I.J.
AU - Glahn, D.C.
AU - Huang, H.
AU - Liu, C.
AU - Malhotra, A.K.
AU - Lencz, T.
JO - European Neuropsychopharmacology
PY - 2021
VL - 46
TODO - 10
SP - 1788-1801
PB - Springer Nature BV
SN - 0924-977X
TODO - 10.1038/s41386-021-01023-4
TODO - 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
TODO - 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).
ER -