ArticleScience (New York, N.Y.)2018
Paternally inherited cis-regulatory structural variants are associated with autism.
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In one paragraph
Article in Science (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 3 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
123citing papers in PubMed, 3 pooled it
16.8field-weighted citation impact, top 1% of its field
What it found
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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.
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.
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Who cites it
123 citing papers in PubMed, 3 syntheses or guidelines pooled it, 217 citations in OpenAlex.
- A systematic review of non-coding RNA genes with differential expression profiles associated with autism spectrum disorders.PloS one · 2023Pooled it
- Rare coding variation provides insight into the genetic architecture and phenotypic context of autism.Nature genetics · 2022Pooled it
- Comprehensive multi-omics integration identifies differentially active enhancers during human brain development with clinical relevance.Genome medicine · 2021Pooled it
- Regulation of RNA transcript elongation in metazoans and its relevance to disease.Nature reviews. Molecular cell biology · 2026Review
- Article
- Illuminating hidden genetic architecture in autism.Cell genomics · 2026Article
- Long-read genome sequencing improves detection and functional interpretation of structural and repeat variants in autism.Cell genomics · 2026Article
- Genetic analysis of neurodegenerative diseases.The Journal of clinical investigation · 2026Review
- Article
- LEO1 haploinsufficiency is associated with developmental delays and autism spectrum disorder.Journal of human genetics · 2026Article
- Article
- Generation and characterization of a knockout mouse of an enhancer of EBF3.Biology open · 2025Article
- Complex de novo structural variants are an underestimated cause of rare disorders.Nature communications · 2025Article
- SDFA: a standardized decomposition format and toolkit for efficient analysis of structural variants in large-scale population genomic studies.Genome biology · 2025Article
- Long read whole genome sequencing-based discovery of structural variants and their role in aetiology of non-syndromic autism spectrum disorder in India.BMC medical genomics · 2025Article
- Pooled, Long-read Sequencing for Structural Variant Characterization in Schistosome Populations.Genome biology and evolution · 2025Article
- Diversity and consequences of structural variation in the human genome.Nature reviews. Genetics · 2025Review
- Categorical misalignment: Making autism(s) in big data biobanking.Social studies of science · 2025Article
- Inter-chromosomal insertions at Xq27.1 associated with retinal dystrophy induce dysregulation of LINC00632 and CDR1as/ciRS-7.American journal of human genetics · 2025Article
- Systematic assessment of structural variant annotation tools for genomic interpretation.Life science alliance · 2025Article
63 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
42 authors at 13 institutions in 5 countries.
William M BrandlerBeyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0001-5280-325X
Danny AntakiBeyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0003-0381-7801
Madhusudan GujralBeyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0001-5010-4826
Morgan L KleiberBeyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-9241-642X
Joe WhitneyThe Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, Canada.ORCID 0000-0001-7389-260X
Michelle S MaileBeyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0003-1045-0825
Oanh HongBeyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0003-4196-4749
Timothy R ChapmanBeyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
Shirley TanBeyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
Prateek TandonBeyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
Timothy PangBeyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.
Shih C TangBeyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-2005-313X
Keith K VauxDepartment of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Yan YangOxford Nanopore Technologies, Inc., NY 10013, USA.
Eoghan HarringtonOxford Nanopore Technologies, Inc., NY 10013, USA.ORCID 0000-0002-4850-2486
Sissel JuulOxford Nanopore Technologies, Inc., NY 10013, USA.ORCID 0000-0002-0315-4449
Daniel J TurnerOxford Nanopore Technologies Ltd., Oxford, UK.ORCID 0000-0002-9716-3169
Bhooma ThiruvahindrapuramThe Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
Gaganjot KaurThe Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, Canada.ORCID 0000-0001-7101-3990
Zhuozhi WangThe Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, Canada.
Stephen F KingsmoreRady Children's Institute for Genomic Medicine, Rady Children's Hospital, San Diego, CA 92123, USA.ORCID 0000-0002-3758-4631
Joseph G GleesonHoward Hughes Medical Institute, Rady Children's Institute of Genomic Medicine, Department of Neurosciences, University of California San Diego, La Jolla, CA 92093, USA.
Denis BissonHuman Longevity, Inc., San Diego, CA 92121, USA.ORCID 0000-0003-0154-9305
Boyko KakaradovHuman Longevity, Inc., San Diego, CA 92121, USA.ORCID 0000-0002-6109-7390
Amalio TelentiHuman Longevity, Inc., San Diego, CA 92121, USA.ORCID 0000-0001-6290-7677
J Craig VenterHuman Longevity, Inc., San Diego, CA 92121, USA.ORCID 0000-0002-7086-765X
Roser CorominasGenetics Unit, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.ORCID 0000-0001-8888-5402
Claudio TomaDepartament de Genètica, Microbiologia i Estadística, Facultat de Biologia, Universitat de Barcelona, Catalonia, Spain.
Bru CormandCentro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain.
Isabel RuedaDepartment of Psychiatry, Hospital Sant Joan de Déu, Barcelona, Spain.ORCID 0000-0002-0844-0591
Silvina GuijarroChild and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Barcelona, Spain.ORCID 0000-0002-9187-1316
Karen S MesserDivision of Biostatistics and Bioinformatics, Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-9298-2413
Caroline M NievergeltDepartment of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.
Maria J ArranzResearch Laboratory Unit, Fundacio Docencia I Recerca Mutua Terrassa, Barcelona, Spain.ORCID 0000-0002-6757-9198
Eric CourchesneAutism Center of Excellence, Department of Neuroscience, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-3772-5799
Karen PierceAutism Center of Excellence, Department of Neuroscience, University of California San Diego, La Jolla, CA 92093, USA.
Alysson R MuotriDepartment of Cellular and Molecular Medicine and Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0003-0867-2875
Lilia M IakouchevaDepartment of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-4542-5219
Amaia HervasChild and Adolescent Mental Health Unit, Hospital Universitari Mútua de Terrassa, Barcelona, Spain.
Stephen W SchererThe Centre for Applied Genomics, Genetics, and Genome Biology, The Hospital for Sick Children, Toronto, Canada.ORCID 0000-0002-8326-1999
Christina CorselloDepartment of Psychiatry, University of California San Diego, La Jolla, CA 92093, USA.ORCID 0000-0002-0572-4249
Jonathan SebatBeyster Center for Genomics of Psychiatric Diseases, University of California San Diego, La Jolla, CA 92093, USA. jsebat@ucsd.edu.ORCID 0000-0002-9087-526X
University of California San Diego · USHospital for Sick Children · CAOxford Nanopore Technologies (United Kingdom) · GBHuman Longevity (United States) · USChildren’s Institute · USMútua Terrassa · ESCentre for Biomedical Network Research on Rare Diseases · ESHospital Sant Joan de Déu Barcelona · ESJ. Craig Venter Institute · USUniversitat Pompeu Fabra · ESUniversity Hospital Mútua de Terrassa · ESUniversity of Toronto · CAUNSW Sydney · AU
Funding
TARGETING GENETIC PATHWAYS FOR BRAIN OVERGROWTH IN AUTISM SPECTRUM DISORDERSP50MH081755 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COURCHESNE, ERIC · 2007 to 2013
$10.3MTraining Program in Basic Clinical GeneticsT32GM008666 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMILTON, BRUCE A · 1998 to 2021
$8.6MConProject-001U19HD077693 · NICHD · RADY PEDIATRIC GENOMICS & SYSTEMS MEDICINE INSTITUTE · PI KINGSMORE, STEPHEN FRANCIS · 2013 to 2018
$6.2MThe Role of Germline Mutation and Parental Age in Autism Spectrum DisordersR01MH076431 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SEBAT, JONATHAN · 2005 to 2015
$5.5MExpanding the accessible genetic architecture of autism by single molecule sequencingR01MH113715 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SEBAT, JONATHAN · 2017 to 2021
$4.1MDevelopmental Functional Genomics in ASD ToddlersR01MH110558 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COURCHESNE, ERIC, LEWIS, NATHAN ENOCH · 2016 to 2020
$3.0MIntegrative functional genomic study of pathways impacted by recurrent autism CNVR01MH108528 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IAKOUCHEVA, LILIA M, MUOTRI, ALYSSON R. · 2016 to 2020
$2.6MEvaluating the effect of splicing mutations on isoform networks in autismR01MH109885 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IAKOUCHEVA, LILIA M, MUOTRI, ALYSSON R. · 2016 to 2020
$2.5MA computational framework for predicting the impact of mutations in autismR01MH105524 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IAKOUCHEVA, LILIA M, RADIVOJAC, PREDRAG · 2014 to 2016
$1.4MProtein network of high risk copy number variants for psychiatric disordersR21MH104766 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IAKOUCHEVA, LILIA M · 2014 to 2015
$421kNICHD NIH HHS U19 HD077693NIGMS NIH HHS T32 GM008666NIMH NIH HHS P50 MH081755NIMH NIH HHS R01 MH076431NIMH NIH HHS R01 MH105524NIMH NIH HHS R01 MH108528NIMH NIH HHS R01 MH109885NIMH NIH HHS R01 MH110558NIMH NIH HHS R01 MH113715NIMH NIH HHS R21 MH104766
Abstract
The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural selection and transmission distortion of CRE-SVs in whole genomes of 9274 subjects from 2600 families affected by ASD. In a discovery cohort of 829 families, structural variants were depleted within promoters and untranslated regions, and paternally inherited CRE-SVs were preferentially transmitted to affected offspring and not to their unaffected siblings. The association of paternal CRE-SVs was replicated in an independent sample of 1771 families. Our results suggest that rare inherited noncoding variants predispose children to ASD, with differing contributions from each parent.
Indexed as
Genetic Predisposition to DiseaseGenetic VariationPaternal InheritanceAutism Spectrum DisorderExonsGene Expression RegulationGenome, HumanHumansMutationPedigreePromoter Regions, GeneticRNA, UntranslatedSelection, GeneticSequence DeletionTranscription FactorsLEO1 protein, humanRNA, UntranslatedTranscription Factors
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