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

doi:10.1038/ncomms5074

Access Status

Open access via publisher

Authors

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

Date

2014

Type

Journal Article

Metadata

Show full item record

Citation

Hadley, 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.

Source Title

Nature Communications

DOI

10.1038/ncomms5074

ISSN

2041-1723

School

School of Occupational Therapy and Social Work

URI

http://hdl.handle.net/20.500.11937/59455

Collection

Curtin Research Publications

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.