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The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism

2014-06-13Journal article Open access
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dc.contributor.authorHadley, D.
dc.contributor.authorWu, Z.L.
dc.contributor.authorKao, C.
dc.contributor.authorKini, A.
dc.contributor.authorMohamed-Hadley, A.
dc.contributor.authorThomas, K.
dc.contributor.authorVazquez, L.
dc.contributor.authorQiu, H.
dc.contributor.authorMentch, F.
dc.contributor.authorPellegrino, R.
dc.contributor.authorKim, C.
dc.contributor.authorConnolly, J.
dc.contributor.authorGlessner, J.
dc.contributor.authorHakonarson, H.
dc.contributor.authorPinto, D.
dc.contributor.authorMerikangas, A.
dc.contributor.authorKlei, L.
dc.contributor.authorVorstman, J.A.
dc.contributor.authorThompson, A.
dc.contributor.authorRegan, R.
dc.contributor.authorPagnamenta, A.T.
dc.contributor.authorOliveira, B.
dc.contributor.authorMagalhaes, T.R.
dc.contributor.authorGilbert, J.
dc.contributor.authorDuketis, E.
dc.contributor.authorDe Jonge, M.V.
dc.contributor.authorCuccaro, M.
dc.contributor.authorCorreia, C.T.
dc.contributor.authorConroy, J.
dc.contributor.authorConceição, I.C.
dc.contributor.authorChiocchetti, A.G.
dc.contributor.authorCasey, J.P.
dc.contributor.authorBolshakova, N.
dc.contributor.authorBacchelli, E.
dc.contributor.authorAnney, R.
dc.contributor.authorZwaigenbaum, L.
dc.contributor.authorWittemeyer, K.
dc.contributor.authorWallace, S.
dc.contributor.authorEngeland, Hv
dc.contributor.authorSoorya, L.
dc.contributor.authorRogé, B.
dc.contributor.authorRoberts, W.
dc.contributor.authorPoustka, F.
dc.contributor.authorMouga, S.
dc.contributor.authorMinshew, N.
dc.contributor.authorMcGrew, S.G.
dc.contributor.authorLord, C.
dc.contributor.authorLeboyer, M.
dc.contributor.authorLe Couteur, A.S.
dc.contributor.authorKolevzon, A.
dc.contributor.authorJacob, S.
dc.contributor.authorGuter, S.
dc.contributor.authorGreen, J.
dc.contributor.authorGreen, A.
dc.contributor.authorGillberg, C.
dc.contributor.authorFernandez, B.A.
dc.contributor.authorDuque, F.
dc.contributor.authorDelorme, R.
dc.contributor.authorDawson, G.
dc.contributor.authorCafé, C.
dc.contributor.authorBrennan, S.
dc.contributor.authorBourgeron, T.
dc.contributor.authorBolton, P.F.
dc.contributor.authorBölte, S.
dc.contributor.authorBernier, R.
dc.contributor.authorBaird, G.
dc.contributor.authorBailey, A.J.
dc.contributor.authorAnagnostou, E.
dc.contributor.authorAlmeida, J.
dc.contributor.authorWijsman, E.M.
dc.contributor.authorVieland, V.J.
dc.contributor.authorVicente, A.M.
dc.contributor.authorSchellenberg, G.D.
dc.contributor.authorPericak-Vance, M.
dc.contributor.authorPaterson, A.D.
dc.contributor.authorParr, J.R.
dc.contributor.authorOliveira, G.
dc.contributor.authorAlmeida, J.
dc.contributor.authorCafé, C.
dc.contributor.authorMouga, S.
dc.contributor.authorCorreia, C.
dc.contributor.authorNurnberger, J.I.
dc.contributor.authorMonaco, A.P.
dc.contributor.authorMaestrini, E.
dc.contributor.authorKlauck, S.M.
dc.contributor.authorHakonarson, H.
dc.contributor.authorHaines, J.L.
dc.contributor.authorGeschwind, D.H.
dc.contributor.authorFreitag, C.M.
dc.contributor.authorFolstein, S.E.
dc.contributor.authorEnnis, S.
dc.contributor.authorCoon, H.
dc.contributor.authorBattaglia, A.
dc.contributor.authorSzatmari, P.
dc.contributor.authorSutcliffe, J.S.
dc.contributor.authorHallmayer, J.
dc.contributor.authorGill, M.
dc.contributor.authorCook, E.H.
dc.contributor.authorBuxbaum, J.D.
dc.contributor.authorDevlin, B.
dc.contributor.authorGallagher, L.
dc.contributor.authorBetancur, C.
dc.contributor.authorScherer, S.W.
dc.date.accessioned2014-10-30T17:25:47Z
dc.date.available2014-10-30T17:25:47Z
dc.date.issued2014-06-13
dc.description.abstractAlthough multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E-09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E-23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions.por
dc.identifier.citationNat Commun. 2014 Jun 13;5:4074. doi: 10.1038/ncomms5074.por
dc.identifier.doincomms5074
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/10400.18/2440
dc.language.isoengpor
dc.peerreviewedyespor
dc.publisherNature Publishing Group: Nature Communicationspor
dc.relation.publisherversionNat Commun. 2014 Jun 13;5:4074. doi: 10.1038/ncomms5074.por
dc.subjectPerturbações do Desenvolvimento Infantil e Saúde Mentalpor
dc.subjectAutismpor
dc.titleThe impact of the metabotropic glutamate receptor and other gene family interaction networks on autismpor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage4074por
oaire.citation.startPage4074por
oaire.citation.titleNature Communicationspor
rcaap.rightsopenAccesspor
rcaap.typearticlepor

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