ArticleMolecular psychiatry2014
Excess of rare novel loss-of-function variants in synaptic genes in schizophrenia and autism spectrum disorders.
Article in Molecular psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 3 of them syntheses that pooled it.
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Who cites it
105 citing papers in PubMed, 3 syntheses or guidelines pooled it, 193 citations in OpenAlex.
- The Autism-Psychosis Continuum Conundrum: Exploring the Role of the Endocannabinoid System.International journal of environmental research and public health · 2022Pooled it
- Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder.Molecular psychiatry · 2021Pooled it
- Genetic variability in scaffolding proteins and risk for schizophrenia and autism-spectrum disorders: a systematic review.Journal of psychiatry & neuroscience : JPN · 2018Pooled it
- Neuregulin1 types mRNA level changes in autism spectrum disorder, and is associated with deficit in executive functions.EBioMedicine · 2018Trial
- Arbaclofen in Children and Adolescents with Autism Spectrum Disorder: A Randomized, Controlled, Phase 2 Trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Trial
- Psychotic Spectrum Symptoms in Adults with Autism Spectrum Disorder and in Their First-Degree Relatives.Brain sciences · 2026Article
- Global developmental delay and focal seizures in individuals with de novo truncating MACF1 variants.Human genomics · 2026Article
- Joint analysis ofNAR genomics and bioinformatics · 2025Article
- GRIN2B-related neurodevelopmental disorders: genotype-phenotype correlations and therapeutic implications.Orphanet journal of rare diseases · 2025Article
- A clinical and genotype-phenotype analysis of MACF1 variants.American journal of human genetics · 2025Article
- NR3C1-mediated epigenetic regulation suppresses astrocytic immune responses in mice.Nature communications · 2025Article
- Domain specific phenotypic expansion associated with variants inmedRxiv : the preprint server for health sciences · 2025Article
- Central role of regular firing neurons of centrolateral amygdala in affective behaviors.iScience · 2025Article
- Loneliness and susceptibility to social pain mediate the association between autistic traits and psychotic experiences in young non-clinical adults.Scientific reports · 2025Article
- Article
- Beyond vertebrates:Frontiers in psychiatry · 2025Review
- Review
- FMR1 genetically interacts with DISC1 to regulate glutamatergic synaptogenesis.Schizophrenia (Heidelberg, Germany) · 2024Article
- NMDA Receptors in Neurodevelopmental Disorders: Pathophysiology and Disease Models.International journal of molecular sciences · 2024Review
- Astrocytic neuroligin 3 regulates social memory and synaptic plasticity through adenosine signaling in male mice.Nature communications · 2024Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Schizophrenia (SZ) and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders that may share an underlying pathology suggested by shared genetic risk variants. We sequenced the exonic regions of 215 genes in 147 ASD cases, 273 SZ cases and 287 controls, to identify rare risk mutations. Genes were primarily selected for their function in the synapse and were categorized as: (1) Neurexin and Neuroligin Interacting Proteins, (2) Post-synaptic Glutamate Receptor Complexes, (3) Neural Cell Adhesion Molecules, (4) DISC1 and Interactors and (5) Functional and Positional Candidates. Thirty-one novel loss-of-function (LoF) variants that are predicted to severely disrupt protein-coding sequence were detected among 2 861 rare variants. We found an excess of LoF variants in the combined cases compared with controls (P=0.02). This effect was stronger when analysis was limited to singleton LoF variants (P=0.0007) and the excess was present in both SZ (P=0.002) and ASD (P=0.001). As an individual gene category, Neurexin and Neuroligin Interacting Proteins carried an excess of LoF variants in cases compared with controls (P=0.05). A de novo nonsense variant in GRIN2B was identified in an ASD case adding to the growing evidence that this is an important risk gene for the disorder. These data support synapse formation and maintenance as key molecular mechanisms for SZ and ASD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.