ArticleCell reports2014
De novo insertions and deletions of predominantly paternal origin are associated with autism spectrum disorder.
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Article in Cell reports, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 3 of them syntheses that pooled it.
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101citing papers in PubMed, 3 pooled it
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Who cites it
101 citing papers in PubMed, 3 syntheses or guidelines pooled it, 181 citations in OpenAlex.
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- Rare coding variation provides insight into the genetic architecture and phenotypic context of autism.Nature genetics · 2022Pooled it
- Common genetic risk variants identified in the SPARK cohort support DDHD2 as a candidate risk gene for autism.Translational psychiatry · 2020Pooled it
- Rationale and Methods for the Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism Center at Columbia University.Pediatric research · 2026Article
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- Mll5 haploinsufficiency attenuates microglial phagocytosis through dysregulated TREM2-SGK3-GSK3β signaling and recapitulates ASD-like behaviors in mice.Nature communications · 2026Article
- Clinical immunology in chromatinopathies: a scoping review.Frontiers in immunology · 2026Article
- Generation and characterization of a knockout mouse of an enhancer of EBF3.Biology open · 2025Article
- Enhancing Genetic Insight: Chromosomal Microarray Enhances Understanding of Genetics in Rubinstein-Taybi Syndrome.Molecular syndromology · 2025Article
- Autism risk genes converge onbioRxiv : the preprint server for biology · 2025Article
- Recent Developments in the Application of Artificial Intelligence and Machine Learning in Early Screening and Diagnosis of Autism.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Sex-Differential Gene Expression in Developing Human Cortex and Its Intersection With Autism Risk Pathways.Biological psychiatry global open science · 2024Article
- Clinical and genetic analysis of a case of OZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Article
- Defining Biological and Biochemical Functions of Noncanonical SET Domain Proteins.Journal of molecular biology · 2024Review
- Proteome-Wide Assessment of Clustering of Missense Variants in Neurodevelopmental Disorders Versus Cancer.medRxiv : the preprint server for health sciences · 2024Article
- Reanalysis of Trio Whole-Genome Sequencing Data Doubles the Yield in Autism Spectrum Disorder: De Novo Variants Present in Half.International journal of molecular sciences · 2024Article
- Comparison of three bioinformatics tools in the detection of ASD candidate variants from whole exome sequencing data.Scientific reports · 2023Article
- The contributions of rare inherited and polygenic risk to ASD in multiplex families.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Phenotypic screening models for rapid diagnosis of genetic variants and discovery of personalized therapeutics.Molecular aspects of medicine · 2023Review
- Candidate biomarkers in psychiatric disorders: state of the field.World psychiatry : official journal of the World Psychiatric Association (WPA) · 2023Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
31 authors at 8 institutions in 2 countries.
Shan DongCenter for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China; Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
Michael F WalkerDepartment of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA.
Nicholas J CarrieroBiomedical High Performance Computing Center, W.M. Keck Biotechnology Resource Laboratory, Department of Computer Science, Yale University, New Haven, CT 06520, USA.
Michael DiColaBionomics Research and Technology, Environmental and Occupational Health Sciences Institute, Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA.
A Jeremy WillseyDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA.
Adam Y YeCenter for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China; National Institute of Biological Sciences, Beijing 102206, People's Republic of China.
Zainulabedin WaqarChild Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Luis E GonzalezChild Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
John D OvertonYale Center for Genomic Analysis, Yale University School of Medicine, New Haven, CT 06520, USA; Regeneron Genetics Center, 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA.
Stephanie FrahmBionomics Research and Technology, Environmental and Occupational Health Sciences Institute, Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA.
John F KeaneyDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT 06520, USA.
Nicole A TeranChild Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Jeanselle DeaDepartment of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA.
Jeffrey D MandellDepartment of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA.
Vanessa Hus BalDepartment of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA.
Catherine A SullivanChild Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Nicholas M DiLulloChild Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
Rehab O KhalilDepartment of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Research on Children with Special Needs, National Research Center, Cairo 11787, Egypt.
Jake GockleyDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
Zafer YukselDepartment of Medical Genetics, Gulhane Military Medical Academy, Ankara 06010, Turkey.
Sinem M SertelDepartment of Molecular Biology and Genetics, Bilkent University, Ankara 06800, Turkey.
A Gulhan Ercan-SencicekDepartment of Neurosurgery, Yale Neurogenetics Program, Yale University School of Medicine, New Haven, CT 06520, USA.
Abha R GuptaChild Study Center, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA.
Shrikant M ManeYale Center for Genomic Analysis, Yale University School of Medicine, New Haven, CT 06520, USA.
Michael SheldonDepartment of Genetics and the Human Genetics Institute, Rutgers University, 145 Bevier Road, Room 136, Piscataway, NJ 08854, USA.
Andrew I BrooksBionomics Research and Technology, Environmental and Occupational Health Sciences Institute, Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Kathryn RoederDepartment of Statistics, Carnegie Mellon University, Pittsburgh, PA 15213, USA; Ray and Stephanie Lane Center for Computational Biology, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Bernie DevlinDepartment of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Matthew W StateDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA; Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA. Electronic address: matthew.state@ucsf.edu.
Liping WeiCenter for Bioinformatics, State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, People's Republic of China; National Institute of Biological Sciences, Beijing 102206, People's Republic of China. Electronic address: weilp@mail.cbi.pku.edu.cn.
Stephan J SandersDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: stephan.sanders@ucsf.edu.
Yale University · USUniversity of California, San Francisco · USEnvironmental and Occupational Health Sciences Institute · USRutgers, The State University of New Jersey · USBilkent University · TRTurkish Armed Forces · TRUniversity of Pittsburgh · USW. M. Keck Foundation · US
Funding
Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI MEGAN C KING · 1985 to 2026
$85.0MYale University Clinical and Translational Science Award ProgramUL1TR000142 · NCATS · YALE UNIVERSITY · PI SHERWIN, ROBERT S · 2012 to 2015
$31.8MGENETICS AND GENOMICS OF HUMAN DISEASET32HD007149 · NICHD · YALE UNIVERSITY · PI James P Noonan · 1985 to 2026
$8.2MGenetics Association in Schizophrenia and Other DisordersR37MH057881 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DEVLIN, BERNIE · 2013 to 2022
$5.4M4/4 The Autism Sequencing Consortium: Autism gene discovery in the >20,000 exomes (supplement)U01MH100239 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STATE, MATTHEW W. · 2013 to 2015
$3.0MYale University Clinical and Translational Science Award ProgramKL2TR000140 · NCATS · YALE UNIVERSITY · PI SHERWIN, ROBERT S · 2012 to 2015
$2.9MCIHRHoward Hughes Medical InstituteNCATS NIH HHS KL2 TR000140NCATS NIH HHS UL1 TR000142NICHD NIH HHS T32 HD007149NIMH NIH HHS R37 MH057881NIMH NIH HHS U01 MH100239
Abstract
Whole-exome sequencing (WES) studies have demonstrated the contribution of de novo loss-of-function single-nucleotide variants (SNVs) to autism spectrum disorder (ASD). However, challenges in the reliable detection of de novo insertions and deletions (indels) have limited inclusion of these variants in prior analyses. By applying a robust indel detection method to WES data from 787 ASD families (2,963 individuals), we demonstrate that de novo frameshift indels contribute to ASD risk (OR = 1.6; 95% CI = 1.0-2.7; p = 0.03), are more common in female probands (p = 0.02), are enriched among genes encoding FMRP targets (p = 6 × 10(-9)), and arise predominantly on the paternal chromosome (p < 0.001). On the basis of mutation rates in probands versus unaffected siblings, we conclude that de novo frameshift indels contribute to risk in approximately 3% of individuals with ASD. Finally, by observing clustering of mutations in unrelated probands, we uncover two ASD-associated genes: KMT2E (MLL5), a chromatin regulator, and RIMS1, a regulator of synaptic vesicle release.
Indexed as
Frameshift MutationSequence DeletionChildChild Development Disorders, PervasiveDNADNA-Binding ProteinsFemaleFragile X Messenger Ribonucleoprotein 1GTP-Binding ProteinsHumansMaleNerve Tissue ProteinsPedigreePhenotypeSex FactorsDNADNA-Binding ProteinsFMR1 protein, humanFragile X Messenger Ribonucleoprotein 1GTP-Binding ProteinsKMT2E protein, humanNerve Tissue ProteinsRIMS1 protein, human
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