ArticleNature2012
De novo mutations revealed by whole-exome sequencing are strongly associated with autism.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,236 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1,236 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- Presymptomatic Biological, Structural, and Functional Diagnostic Biomarkers of Autism Spectrum Disorder.Journal of neurochemistry · 2025Pooled it
- A assessment of the effects of parental age on the development of autism in children: a systematic review and a meta-analysis.BMC psychology · 2024Pooled it
- In Search of Biomarkers to Guide Interventions in Autism Spectrum Disorder: A Systematic Review.The American journal of psychiatry · 2023Pooled it
- Functional and pharmacological characterization of theEpilepsy & behavior reports · 2026Article
- Nonsense-mediated decay influences position-dependent effects of SCN2A premature stop codons on neuronal excitability and behavior.Molecular psychiatry · 2026Article
- PACS1 syndrome variant alters the proteomic landscape of developing cortical organoids.iScience · 2026Article
- Genetic architecture of postpartum psychosis: from common to rare genetic variation.Molecular psychiatry · 2026Article
- Autism-associated SCN2A deficiency disrupts cortico-striatal circuitry in human brain assembloids.Neuron · 2026Article
- Gene therapy with doxycycline-controlled expression of human Kv1.1 reduces neuronal excitability and increases sociability ofbioRxiv : the preprint server for biology · 2026Article
- Maternal age as a driver of genome instability: mechanisms linking aneuploidy, mutagenesis and mitochondrial dysfunction.Archives of toxicology · 2026Review
- ASD mutations in the ciliary gene CEP41 impact development of projection neurons and interneurons in a human cortical organoid model.Molecular psychiatry · 2026Article
- Whole-exome sequencing in individuals with obsessive-compulsive disorder and chronic tic disorders identifies 36 large-effect risk genes.Nature neuroscience · 2026Article
- Heterozygous Variants in LRP1 Cause a Neurodevelopmental Disorder With Congenital Heart Defects.American journal of medical genetics. Part A · 2026Article
- Cognitive and synaptic impairment induced by deficiency of autism risk gene Smarcc2 and its rescue by histone deacetylase inhibition.Molecular psychiatry · 2026Article
- Loss of Zmiz1 in Mice Leads to Impaired Cortical Development and Autistic-Like Behaviors.Biological psychiatry · 2026Article
- Challenging the Developmental Substructure Model for Autism: A Perspective From Causal Statistics.Autism research : official journal of the International Society for Autism Research · 2026Article
- Article
- A Developmental Neuroimmune Cascade Model of Autism Spectrum Disorder.International journal of molecular sciences · 2026Review
- Functional Genomics Studies of Psychiatric Disorders in Individuals of Latin American Populations: A Scoping Review.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2026Article
- Temporal and Cell-Specific Regulation of Synaptic Homeostasis by the Chromatin Remodeler Chd1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
1,176 more citing papers are in PubMed but not listed here.
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Authors and funding
30 authors.
Funding
Abstract
Multiple studies have confirmed the contribution of rare de novo copy number variations to the risk for autism spectrum disorders. But whereas de novo single nucleotide variants have been identified in affected individuals, their contribution to risk has yet to be clarified. Specifically, the frequency and distribution of these mutations have not been well characterized in matched unaffected controls, and such data are vital to the interpretation of de novo coding mutations observed in probands. Here we show, using whole-exome sequencing of 928 individuals, including 200 phenotypically discordant sibling pairs, that highly disruptive (nonsense and splice-site) de novo mutations in brain-expressed genes are associated with autism spectrum disorders and carry large effects. On the basis of mutation rates in unaffected individuals, we demonstrate that multiple independent de novo single nucleotide variants in the same gene among unrelated probands reliably identifies risk alleles, providing a clear path forward for gene discovery. Among a total of 279 identified de novo coding mutations, there is a single instance in probands, and none in siblings, in which two independent nonsense variants disrupt the same gene, SCN2A (sodium channel, voltage-gated, type II, α subunit), a result that is highly unlikely by chance.
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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.