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dc.contributor.authorHadley, D.
dc.contributor.authorWu, Z.
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.
dc.contributor.authorThompson, A.
dc.contributor.authorRegan, R.
dc.contributor.authorPagnamenta, A.
dc.contributor.authorOliveira, B.
dc.contributor.authorMagalhaes, T.
dc.contributor.authorGilbert, J.
dc.contributor.authorDuketis, E.
dc.contributor.authorDe Jonge, M.
dc.contributor.authorCuccaro, M.
dc.contributor.authorCorreia, C.
dc.contributor.authorConroy, J.
dc.contributor.authorConceiça, I.
dc.contributor.authorChiocchetti, A.
dc.contributor.authorCasey, J.
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.authorVan Engeland, H.
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.
dc.contributor.authorLord, C.
dc.contributor.authorLeboyer, M.
dc.contributor.authorLe Couteur, A.
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.
dc.contributor.authorDuque, F.
dc.contributor.authorDelorme, R.
dc.contributor.authorDawson, G.
dc.contributor.authorBrennan, S.
dc.contributor.authorBourgeron, T.
dc.contributor.authorBolton, P.
dc.contributor.authorBolte, Sven
dc.date.accessioned2017-12-10T12:40:16Z
dc.date.available2017-12-10T12:40:16Z
dc.date.created2017-12-10T12:20:20Z
dc.date.issued2014
dc.identifier.citationHadley, D. and Wu, Z. and Kao, C. and Kini, A. and Mohamed-Hadley, A. and Thomas, K. and Vazquez, L. et al. 2014. The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism. Nature Communications. 5.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/59455
dc.identifier.doi10.1038/ncomms5074
dc.description.abstract

Although 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 4.16 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. © 2014 Macmillan Publishers Limited. All rights reserved.

dc.publisherMacmillan Publishers Limited
dc.titleThe impact of the metabotropic glutamate receptor and other gene family interaction networks on autism
dc.typeJournal Article
dcterms.source.volume5
dcterms.source.issn2041-1723
dcterms.source.titleNature Communications
curtin.departmentSchool of Occupational Therapy and Social Work
curtin.accessStatusOpen access via publisher


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