ArticleProceedings of the National Academy of Sciences of the United States of America2016
Increased burden of deleterious variants in essential genes in autism spectrum disorder.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- A multifaceted approach for analyzing complex phenotypic data in rodent models of autism.Molecular autism · 2019Pooled it
- Evolutionarily new genes in humans with disease phenotypes reveal functional enrichment patterns shaped by adaptive innovation and sexual selection.bioRxiv : the preprint server for biology · 2024Article
- Evolutionarily new genes in humans with disease phenotypes reveal functional enrichment patterns shaped by adaptive innovation and sexual selection.Research square · 2023Article
- Essential genes: a cross-species perspective.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Chromatin regulators in the TBX1 network confer risk for conotruncal heart defects in 22q11.2DS.NPJ genomic medicine · 2023Article
- Identifying rare genetic variants in 21 highly multiplex autism families: the role of diagnosis and autistic traits.Molecular psychiatry · 2023Article
- Evidence of epistasis in regions of long-range linkage disequilibrium across five complex diseases in the UK Biobank and eMERGE datasets.American journal of human genetics · 2023Article
- Gene burden analysis identifies genes associated with increased risk and severity of adult-onset hearing loss in a diverse hospital-based cohort.PLoS genetics · 2023Article
- Improper Proteostasis: Can It Serve as Biomarkers for Neurodegenerative Diseases?Molecular neurobiology · 2022Review
- Leveraging gene co-regulation to identify gene sets enriched for disease heritability.American journal of human genetics · 2022Article
- Developmental disorders caused by haploinsufficiency of transcriptional regulators: a perspective based on cell fate determination.Biology open · 2022Article
- Computational approaches for predicting variant impact: An overview from resources, principles to applications.Frontiers in genetics · 2022Review
- Evolution and dysfunction of human cognitive and social traits: A transcriptional regulation perspective.Evolutionary human sciences · 2022Review
- Prioritization of schizophrenia risk genes from GWAS results by integrating multi-omics data.Translational psychiatry · 2021Article
- Analysis of Stop Codons within Prokaryotic Protein-Coding Genes Suggests Frequent Readthrough Events.International journal of molecular sciences · 2021Article
- Expression Analysis of Ermin and Listerin E3 Ubiquitin Protein Ligase 1 Genes in Autistic Patients.Frontiers in molecular neuroscience · 2021Article
- An Automated Functional Annotation Pipeline That Rapidly Prioritizes Clinically Relevant Genes for Autism Spectrum Disorder.International journal of molecular sciences · 2020Article
- Excess of singleton loss-of-function variants in Parkinson's disease contributes to genetic risk.Journal of medical genetics · 2020Article
- Characterization of Single Gene Copy Number Variants in Schizophrenia.Biological psychiatry · 2020Article
- Germline burden of rare damaging variants negatively affects human healthspan and lifespan.eLife · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Autism spectrum disorder (ASD) is a heterogeneous, highly heritable neurodevelopmental syndrome characterized by impaired social interaction, communication, and repetitive behavior. It is estimated that hundreds of genes contribute to ASD. We asked if genes with a strong effect on survival and fitness contribute to ASD risk. Human orthologs of genes with an essential role in pre- and postnatal development in the mouse [essential genes (EGs)] are enriched for disease genes and under strong purifying selection relative to human orthologs of mouse genes with a known nonlethal phenotype [nonessential genes (NEGs)]. This intolerance to deleterious mutations, commonly observed haploinsufficiency, and the importance of EGs in development suggest a possible cumulative effect of deleterious variants in EGs on complex neurodevelopmental disorders. With a comprehensive catalog of 3,915 mammalian EGs, we provide compelling evidence for a stronger contribution of EGs to ASD risk compared with NEGs. By examining the exonic de novo and inherited variants from 1,781 ASD quartet families, we show a significantly higher burden of damaging mutations in EGs in ASD probands compared with their non-ASD siblings. The analysis of EGs in the developing brain identified clusters of coexpressed EGs implicated in ASD. Finally, we suggest a high-priority list of 29 EGs with potential ASD risk as targets for future functional and behavioral studies. Overall, we show that large-scale studies of gene function in model organisms provide a powerful approach for prioritization of genes and pathogenic variants identified by sequencing studies of human disease.
Indexed as
Identifiers
What OpenQuestion holds
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.