publication . Other literature type . Article . 2014

De novo mutations in schizophrenia implicate synaptic networks

Menachem Fromer; Andrew J. Pocklington; David H. Kavanagh; Hywel J. Williams; Sarah Dwyer; Padhraig Gormley; Lyudmila Georgieva; Elliott Rees; Priit Palta; Douglas M. Ruderfer; ...
  • Published: 22 Jan 2014
  • Publisher: Springer Science and Business Media LLC
Abstract
Inherited alleles account for most of the genetic risk for schizophrenia. However, new (de novo) mutations, in the form of large chromosomal copy number changes, occur in a small fraction of cases and disproportionally disrupt genes encoding postsynaptic proteins. Here we show that small de novo mutations, affecting one or a few nucleotides, are overrepresented among glutamatergic postsynaptic proteins comprising activity-regulated cytoskeleton-associated protein (ARC) and N-methyl-d-aspartate receptor (NMDAR) complexes. Mutations are additionally enriched in proteins that interact with these complexes to modulate synaptic strength, namely proteins regulating ac...
Subjects
free text keywords: Article, Multidisciplinary, Exome, Allele, Phenotype, Postsynaptic potential, Biology, Genetics, Mutation, medicine.disease_cause, medicine, Copy-number variation, Gene, Mutation rate
Funded by
NIH| Software for the analysis of large-scale genotyping and sequencing studies
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01HG005827-04
  • Funding stream: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
,
EC| GEUVADIS
Project
GEUVADIS
Sharing capacity across Europe in high-throughput sequencing technology to explore genetic variation in health and disease
  • Funder: European Commission (EC)
  • Project Code: 261123
  • Funding stream: FP7 | SP1 | HEALTH
,
WT| Genetics of common neurological diseases.
Project
  • Funder: Wellcome Trust (WT)
  • Project Code: 089062
  • Funding stream: Cellular and Molecular Neuroscience
,
NIH| P3- PTPRZ1 signaling in schizophrenia
Project
  • Funder: National Institutes of Health (NIH)
  • Project Code: 3P50MH066392-09S1
  • Funding stream: NATIONAL INSTITUTE OF MENTAL HEALTH
,
EC| EU-GEI
Project
EU-GEI
European Network of National Schizophrenia Networks Studying Gene-Environment Interactions
  • Funder: European Commission (EC)
  • Project Code: 241909
  • Funding stream: FP7 | SP1 | HEALTH
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