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

We just began a large new study on
Autism, ADHD, Anxiety & Depression in 12-17 year-olds.
Read more and learn how you can help!

TitleThe impact of the metabotropic glutamate receptor and other gene family interaction networks on autism.
Publication TypeJournal Article
Year of Publication2014
AuthorsHadley, 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, Glessner, J, Hakonarson, H
Corporate AuthorsAGP Consortium
JournalNat Commun
Volume5
Pagination4074
Date Published2014 Jun 13
ISSN2041-1723
KeywordsAutistic Disorder, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Calmodulin, Child, Child, Preschool, DNA Copy Number Variations, Female, Gene Regulatory Networks, Humans, Male, Proto-Oncogene Proteins c-myc, Receptors, Metabotropic Glutamate
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 ≤ 4.16E-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.

DOI10.1038/ncomms5074
Alternate JournalNat Commun
PubMed ID24927284
PubMed Central IDPMC4059929
Grant ListR01 MH064547 / MH / NIMH NIH HHS / United States
1U24MH081810 / MH / NIMH NIH HHS / United States
MH64547 / MH / NIMH NIH HHS / United States
U01HG005830 / HG / NHGRI NIH HHS / United States
Comments
Leave a Comment