The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism
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 bi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal Article |
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Macmillan Publishers Limited
2014
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| Online Access: | http://hdl.handle.net/20.500.11937/59455 |
| _version_ | 1848760485216780288 |
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| author | Hadley, D. Wu, Z. Kao, C. Kini, A. Mohamed-Hadley, A. Thomas, K. Vazquez, L. Qiu, H. Mentch, F. Pellegrino, R. Kim, C. Connolly, J. Glessner, J. Hakonarson, H. Pinto, D. Merikangas, A. Klei, L. Vorstman, J. Thompson, A. Regan, R. Pagnamenta, A. Oliveira, B. Magalhaes, T. Gilbert, J. Duketis, E. De Jonge, M. Cuccaro, M. Correia, C. Conroy, J. Conceiça, I. Chiocchetti, A. Casey, J. Bolshakova, N. Bacchelli, E. Anney, R. Zwaigenbaum, L. Wittemeyer, K. Wallace, S. Van Engeland, H. Soorya, L. Rogé, B. Roberts, W. Poustka, F. Mouga, S. Minshew, N. McGrew, S. Lord, C. Leboyer, M. Le Couteur, A. Kolevzon, A. Jacob, S. Guter, S. Green, J. Green, A. Gillberg, C. Fernandez, B. Duque, F. Delorme, R. Dawson, G. Brennan, S. Bourgeron, T. Bolton, P. Bolte, Sven |
| author_facet | Hadley, D. Wu, Z. Kao, C. Kini, A. Mohamed-Hadley, A. Thomas, K. Vazquez, L. Qiu, H. Mentch, F. Pellegrino, R. Kim, C. Connolly, J. Glessner, J. Hakonarson, H. Pinto, D. Merikangas, A. Klei, L. Vorstman, J. Thompson, A. Regan, R. Pagnamenta, A. Oliveira, B. Magalhaes, T. Gilbert, J. Duketis, E. De Jonge, M. Cuccaro, M. Correia, C. Conroy, J. Conceiça, I. Chiocchetti, A. Casey, J. Bolshakova, N. Bacchelli, E. Anney, R. Zwaigenbaum, L. Wittemeyer, K. Wallace, S. Van Engeland, H. Soorya, L. Rogé, B. Roberts, W. Poustka, F. Mouga, S. Minshew, N. McGrew, S. Lord, C. Leboyer, M. Le Couteur, A. Kolevzon, A. Jacob, S. Guter, S. Green, J. Green, A. Gillberg, C. Fernandez, B. Duque, F. Delorme, R. Dawson, G. Brennan, S. Bourgeron, T. Bolton, P. Bolte, Sven |
| author_sort | Hadley, D. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T10:16:31Z |
| format | Journal Article |
| id | curtin-20.500.11937-59455 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:16:31Z |
| publishDate | 2014 |
| publisher | Macmillan Publishers Limited |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-594552017-12-10T12:40:16Z The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism Hadley, D. Wu, Z. Kao, C. Kini, A. Mohamed-Hadley, A. Thomas, K. Vazquez, L. Qiu, H. Mentch, F. Pellegrino, R. Kim, C. Connolly, J. Glessner, J. Hakonarson, H. Pinto, D. Merikangas, A. Klei, L. Vorstman, J. Thompson, A. Regan, R. Pagnamenta, A. Oliveira, B. Magalhaes, T. Gilbert, J. Duketis, E. De Jonge, M. Cuccaro, M. Correia, C. Conroy, J. Conceiça, I. Chiocchetti, A. Casey, J. Bolshakova, N. Bacchelli, E. Anney, R. Zwaigenbaum, L. Wittemeyer, K. Wallace, S. Van Engeland, H. Soorya, L. Rogé, B. Roberts, W. Poustka, F. Mouga, S. Minshew, N. McGrew, S. Lord, C. Leboyer, M. Le Couteur, A. Kolevzon, A. Jacob, S. Guter, S. Green, J. Green, A. Gillberg, C. Fernandez, B. Duque, F. Delorme, R. Dawson, G. Brennan, S. Bourgeron, T. Bolton, P. Bolte, Sven 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. 2014 Journal Article http://hdl.handle.net/20.500.11937/59455 10.1038/ncomms5074 Macmillan Publishers Limited unknown |
| spellingShingle | Hadley, D. Wu, Z. Kao, C. Kini, A. Mohamed-Hadley, A. Thomas, K. Vazquez, L. Qiu, H. Mentch, F. Pellegrino, R. Kim, C. Connolly, J. Glessner, J. Hakonarson, H. Pinto, D. Merikangas, A. Klei, L. Vorstman, J. Thompson, A. Regan, R. Pagnamenta, A. Oliveira, B. Magalhaes, T. Gilbert, J. Duketis, E. De Jonge, M. Cuccaro, M. Correia, C. Conroy, J. Conceiça, I. Chiocchetti, A. Casey, J. Bolshakova, N. Bacchelli, E. Anney, R. Zwaigenbaum, L. Wittemeyer, K. Wallace, S. Van Engeland, H. Soorya, L. Rogé, B. Roberts, W. Poustka, F. Mouga, S. Minshew, N. McGrew, S. Lord, C. Leboyer, M. Le Couteur, A. Kolevzon, A. Jacob, S. Guter, S. Green, J. Green, A. Gillberg, C. Fernandez, B. Duque, F. Delorme, R. Dawson, G. Brennan, S. Bourgeron, T. Bolton, P. Bolte, Sven The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism |
| title | The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism |
| title_full | The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism |
| title_fullStr | The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism |
| title_full_unstemmed | The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism |
| title_short | The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism |
| title_sort | impact of the metabotropic glutamate receptor and other gene family interaction networks on autism |
| url | http://hdl.handle.net/20.500.11937/59455 |