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

Publication ,  Journal Article
Hadley, D; Wu, Z-L; Kao, C; Kini, A; Mohamed-Hadley, A; Thomas, K; Vazquez, L; Qiu, H; Mentch, F; Pellegrino, R; Kim, C; Connolly, J ...
Published in: Nat Commun
June 13, 2014

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 ≤ 4.16E-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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 13, 2014

Volume

5

Start / End Page

4074

Location

England

Related Subject Headings

  • Receptors, Metabotropic Glutamate
  • Proto-Oncogene Proteins c-myc
  • Male
  • Humans
  • Gene Regulatory Networks
  • Female
  • DNA Copy Number Variations
  • Child, Preschool
  • Child
  • Calmodulin
 

Citation

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Hadley, D., Wu, Z.-L., Kao, C., Kini, A., Mohamed-Hadley, A., Thomas, K., … Hakonarson, H. (2014). The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism. Nat Commun, 5, 4074. https://doi.org/10.1038/ncomms5074
Hadley, Dexter, Zhi-Liang Wu, Charlly Kao, Akshata Kini, Alisha Mohamed-Hadley, Kelly Thomas, Lyam Vazquez, et al. “The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism.Nat Commun 5 (June 13, 2014): 4074. https://doi.org/10.1038/ncomms5074.
Hadley D, Wu Z-L, Kao C, Kini A, Mohamed-Hadley A, Thomas K, et al. The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism. Nat Commun. 2014 Jun 13;5:4074.
Hadley, Dexter, et al. “The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism.Nat Commun, vol. 5, June 2014, p. 4074. Pubmed, doi:10.1038/ncomms5074.
Hadley D, Wu Z-L, Kao C, Kini A, Mohamed-Hadley A, Thomas K, Vazquez L, Qiu H, Mentch F, Pellegrino R, Kim C, Connolly J, AGP Consortium, Glessner J, Hakonarson H. The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism. Nat Commun. 2014 Jun 13;5:4074.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 13, 2014

Volume

5

Start / End Page

4074

Location

England

Related Subject Headings

  • Receptors, Metabotropic Glutamate
  • Proto-Oncogene Proteins c-myc
  • Male
  • Humans
  • Gene Regulatory Networks
  • Female
  • DNA Copy Number Variations
  • Child, Preschool
  • Child
  • Calmodulin