ArticleGenetics in medicine : official journal of the American College of Medical Genetics2020
Nonrandom occurrence of multiple de novo coding variants in a proband indicates the existence of an oligogenic model in autism.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- New Candidates for Autism/Intellectual Disability Identified by Whole-Exome Sequencing.International journal of molecular sciences · 2021Trial
- MSL2 orchestrates oligodendrocyte precursor cell cycle via H3K4me3 to prevent white matter defects in neurodevelopmental disorders.Experimental & molecular medicine · 2026Article
- Circadian rhythm lncRNABiochemistry and biophysics reports · 2026Article
- Co-occurrence of rare variants implicates gene pairs in cytoskeletal pathways and is associated with increased severity in autism spectrum disorder.Genome biology · 2026Article
- Article
- Individuals with intellectual disability have an increased burden ofmedRxiv : the preprint server for health sciences · 2025Article
- miR-146A and miR-146B Promoter Methylation and Common Sequence Variations Are Not Likely to Be Involved in Autism Spectrum Disorder.Journal of molecular neuroscience : MN · 2025Article
- Clinical Application of a Customized Gene Panel for Identifying Autism Spectrum Disorder-Associated Variants.Medicina (Kaunas, Lithuania) · 2025Article
- Roles of ANK2/ankyrin-B in neurodevelopmental disorders: Isoform functions and implications for autism spectrum disorder and epilepsy.Current opinion in neurobiology · 2025Review
- Association of SCN1A Gene Polymorphisms with Sodium Valproate Resistance in Pediatric Epilepsy: A Retrospective Case-Control Study.Neuropsychiatric disease and treatment · 2025Article
- Lactate Ameliorates Kainic Acid-Induced Neuroinflammation and Cognitive Impairment via the Chemokine Signaling Pathway in Mice.Journal of inflammation research · 2025Article
- MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature.American journal of human genetics · 2024Article
- Statistical methods for assessing the effects of de novo variants on birth defects.Human genomics · 2024Review
- Comparison of three bioinformatics tools in the detection of ASD candidate variants from whole exome sequencing data.Scientific reports · 2023Article
- Three generation families: Analysis of de novo variants in autism.European journal of human genetics : EJHG · 2023Article
- A cryptic microdeletion del(12)(p11.21p11.23) within an unbalanced translocation t(7;12)(q21.13;q23.1) implicates new candidate loci for intellectual disability and Kallmann syndrome.Scientific reports · 2023Article
- Whole Genome Sequencing Revealed Inherited Rare Oligogenic Variants Contributing to Schizophrenia and Major Depressive Disorder in Two Families.International journal of molecular sciences · 2023Article
- Truncating PICK1 Variant Identified in Azoospermia Affected Mitochondrial Dysfunction in Knockout Mice.Current medical science · 2023Article
- A microdeletion del(12)(p11.21p11.23) with a cryptic unbalanced translocation t(7;12)(q21.13;q23.1) implicates new candidate loci for intellectual disability and Kallmann syndrome.Research square · 2023Article
- Identification of two novel autism genes,Frontiers in psychiatry · 2023Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeElucidating the genetic architecture underlying autism spectrum disorder (ASD) will aid in the understanding of its genetic etiology and clinical diagnosis.
methodsA comprehensive set of coding de novo variants (DNVs) from 4504 trios with ASD and 3012 control/sibling trios from several large-scale sequencing studies were collected and combined. Multiple in-depth analyses including DNVs burden, clinical phenotypes, and functional networks underlying the combined data set were used to evaluate the nonrandom occurrence of multiple extreme DNVs (loss-of-function and damaging missense variants) in the same patients.
resultsWe observed a significant excess of multiple extreme DNVs among patients with ASD compared with controls. Meanwhile, patients with ASD carrying 2+ extreme DNVs had significantly lower IQs than patients carrying 0 or 1 DNV. Moreover, much closer functional connectivity than expected was observed among 2 or more genes with extreme DNVs from the same individuals. In particular, we identified 56 key genes as more confident ASD genes compared with other known ASD genes. In addition, we detected 23 new ASD candidate genes with recurrent DNVs, including VIP, ZWILCH, MSL2, LRRC4, and CAPRIN1.
conclusionsOur findings present compelling statistical evidence supporting an oligogenic model and provide new insights into the genetic architecture of ASD.
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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.