ArticleNature communications2020
Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.
Erratum issuedOpen access · goldAbstract readMulticenter Study
In one paragraph
Article in Nature communications, 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 130 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
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130citing papers in PubMed, 2 pooled it
19.8field-weighted citation impact, top 1% of its field
What it found
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Who cites it
130 citing papers in PubMed, 2 syntheses or guidelines pooled it, 209 citations in OpenAlex.
- Neurodevelopmental disorders in childhood-onset hereditary spastic paraplegia type 7: a case series and review of literature.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
- An updated catalog ofFrontiers in molecular neuroscience · 2023Pooled it
- Functional characterization of 42 CK2α de novo variants associated with Okur-Chung neurodevelopmental syndrome.The FEBS journal · 2026Article
- An ASXL3-thyroid hormone axis in parvalbumin interneurons controls autism-like behaviors.Science advances · 2026Article
- BiallelicInternational journal of molecular sciences · 2026Article
- Rationale and Methods for the Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism Center at Columbia University.Pediatric research · 2026Article
- Characterization of the genotypic and phenotypic spectrum of TCF7L2-related neurodevelopmental disorder (TRND).Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
- Charting the human-specific properties of gene expression networks in the infant prefrontal cortex.Science advances · 2026Article
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- Long-read sequencing of families reveals increased germline and postzygotic mutation rates in repetitive DNA.Nature communications · 2026Article
- Shared and distinct phenotypic profiles among neurodevelopmental disorder genes.medRxiv : the preprint server for health sciences · 2026Article
- A xenotransplantation model for reactivation of paternal UBE3A using human-specific antisense oligonucleotides.Scientific reports · 2026Article
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- LEO1 haploinsufficiency is associated with developmental delays and autism spectrum disorder.Journal of human genetics · 2026Article
- Loss of DOT1L disrupts neuronal transcription and leads to a neurodevelopmental disorder.Brain : a journal of neurology · 2026Article
- Longitudinal Characterization of GiantResearch (Washington, D.C.) · 2026Article
- Identification of De NovoInternational journal of pediatrics · 2026Article
- Severity-stratified genetic diagnosis by trio exome sequencing in isolated fetal growth restriction.Frontiers in genetics · 2026Article
- The regulatory role of CASZ1 in keratinocyte differentiation and skin barrier function in atopic dermatitis.Genes & diseases · 2026Article
70 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
72 authors at 20 institutions in 9 countries.
Tianyun WangDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-5179-087X
Kendra HoekzemaDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Davide VecchioRare Disease and Medical Genetics, Academic Department of Pediatrics, Bambino Gesù Children's Hospital, Rome, Italy.ORCID http://orcid.org/0000-0003-2907-3206
Huidan WuCenter for Medical Genetics & Hunan Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Arvis SulovariDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-4354-9020
Bradley P CoeDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Madelyn A GillentineDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-8989-2214
Amy B WilfertDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.
Luis A Perez-JuradoPaediatric and Reproductive Genetics unit, Women's and Children's Hospital, Adelaide, SA, Australia.
Malin KvarnungDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Yoeri SleypCentre for Human Genetics, KU Leuven and Leuven Autism Research (LAuRes), Leuven, Belgium.
Rachel K EarlDepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Jill A RosenfeldDepartment of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0001-5664-7987
Madeleine R GeishekerDepartment of Genome Sciences, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-4166-3236
Lin HanCenter for Medical Genetics & Hunan Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Bing DuCenter for Medical Genetics & Hunan Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Chris BarnettPaediatric and Reproductive Genetics unit, Women's and Children's Hospital, Adelaide, SA, Australia.
Elizabeth ThompsonPaediatric and Reproductive Genetics unit, Women's and Children's Hospital, Adelaide, SA, Australia.
Marie ShawAdelaide Medical School and the Robinson Research Institute, the University of Adelaide, Adelaide, SA, Australia.
Renee CarrollAdelaide Medical School and the Robinson Research Institute, the University of Adelaide, Adelaide, SA, Australia.
Kathryn FriendGenetics and Molecular Pathology, SA Pathology, Adelaide, SA, Australia.
Rachael CatfordGenetics and Molecular Pathology, SA Pathology, Adelaide, SA, Australia.
Elizabeth E PalmerGenetics of Learning Disability Service, Hunter New England Health Service, Waratah, NSW, Australia.
Xiaobing ZouChildren Development Behavior Center, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
Jianjun OuMental Health Institute of the Second Xiangya Hospital, Central South University, Changsha, China.
Honghui LiKey Laboratory of Developmental Disorders in Children, Liuzhou Maternity and Child Healthcare Hospital, Liuzhou, China.
Hui GuoCenter for Medical Genetics & Hunan Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.ORCID http://orcid.org/0000-0002-1570-2545
Jennifer GerdtsDepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Emanuela AvolaOasi Research Institute-IRCCS, Troina, Italy.
Giuseppe CalabreseOasi Research Institute-IRCCS, Troina, Italy.
Maurizio EliaOasi Research Institute-IRCCS, Troina, Italy.
Donatella GrecoOasi Research Institute-IRCCS, Troina, Italy.
Anna LindstrandDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-0806-5602
Ann NordgrenDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.ORCID http://orcid.org/0000-0003-3285-4281
Britt-Marie AnderlidDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Geert VandeweyerDepartment of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Anke Van DijckDepartment of Medical Genetics, University of Antwerp, Antwerp, Belgium.ORCID http://orcid.org/0000-0002-6713-2943
Nathalie Van der AaDepartment of Medical Genetics, University of Antwerp, Antwerp, Belgium.
Brooke McKennaDepartment of Psychology, Emory University, Atlanta, GA, USA.
Miroslava HancarovaDepartment of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
Sarka BendovaDepartment of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
Marketa HavlovicovaDepartment of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
Giovanni MalerbaDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Bernardo Dalla BernardinaChild Neuropsychiatry Unit, AOUI, Verona, Italy.
Pierandrea MugliaUCB Pharma, Bruxelles, Belgium.
Arie van HaeringenDepartment of Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, Netherlands.
Mariette J V HofferDepartment of Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, Netherlands.ORCID http://orcid.org/0000-0002-1812-7670
Barbara FrankeDepartment of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.ORCID http://orcid.org/0000-0003-4375-6572
Gerarda CappuccioDepartment of Translational Medicine, Federico II University, Naples, Italy.
Martin DelatyckiMurdoch Children's Research Institute, Melbourne, Australia.
Paul J LockhartMurdoch Children's Research Institute, Melbourne, Australia.ORCID http://orcid.org/0000-0003-2531-8413
Melanie A ManningDivision of Medical Genetics, Department of Pediatrics, Stanford University, Stanford, CA, USA.
Pengfei LiuDepartment of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA.ORCID http://orcid.org/0000-0002-4177-709X
Ingrid E SchefferMurdoch Children's Research Institute, Melbourne, Australia.
Nicola Brunetti-PierriDepartment of Translational Medicine, Federico II University, Naples, Italy.ORCID http://orcid.org/0000-0002-6895-8819
Nanda RommelseDepartment of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, Netherlands.
David G AmaralDepartment of Psychiatry and Behavioral Sciences and the MIND Institute, University of California, Davis, Sacramento, CA, USA.
Gijs W E SantenDepartment of Clinical Genetics, Leiden University Medical Center (LUMC), Leiden, Netherlands.
Elisabetta TrabettiDepartment of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Verona, Italy.
Zdeněk SedláčekDepartment of Biology and Medical Genetics, Charles University 2nd Faculty of Medicine and University Hospital Motol, Prague, Czech Republic.
Jacob J MichaelsonDepartment of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA, USA.ORCID http://orcid.org/0000-0001-9713-0992
Karen PierceDepartment of Neurosciences, UC San Diego Autism Center, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Eric CourchesneDepartment of Neurosciences, UC San Diego Autism Center, School of Medicine, University of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-3772-5799
R Frank KooyDepartment of Medical Genetics, University of Antwerp, Antwerp, Belgium.ORCID http://orcid.org/0000-0003-2024-0485
SPARK Consortium
Magnus NordenskjöldDepartment of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Corrado RomanoOasi Research Institute-IRCCS, Troina, Italy.ORCID http://orcid.org/0000-0003-1049-0683
Hilde PeetersCentre for Human Genetics, KU Leuven and Leuven Autism Research (LAuRes), Leuven, Belgium.
Raphael A BernierDepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Jozef GeczSouth Australian Health and Medical Research Institute, Adelaide, SA, Australia.ORCID http://orcid.org/0000-0002-7884-6861
Kun XiaCenter for Medical Genetics & Hunan Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.ORCID http://orcid.org/0000-0001-8090-6002
Evan E EichlerDepartment of Genome Sciences, University of Washington, Seattle, WA, USA. eee@gs.washington.edu.ORCID http://orcid.org/0000-0002-8246-4014
Simons Foundation · USUniversity of Washington · USNationwide Children's Hospital · USBoston Children's Hospital · USUniversity of Minnesota · USKennedy Krieger Institute · USRush University Medical Center · USUniversity of California, Los Angeles · USUniversity of Missouri · USOregon Health & Science University · USUniversity of California, Davis · USBaylor College of Medicine · USCentral South University · CNUniversity of Iowa · USUniversity of Miami · USCincinnati Children's Hospital Medical Center · USKarolinska University Hospital · SEOasi Maria SS · ITAutism & Developmental Medicine Institute · USCenter for Autism and Related Disorders · US
Funding
INTERDISCIPLINARY TRAINING IN GENOMIC SCIENCEST32HG000035 · NHGRI · UNIVERSITY OF WASHINGTON · PI Bruce Colston Trapnell · 1995 to 2026
$24.2MMechanisms of Brain Dysmorphology in MN1 C-Terminal Truncation Syndrome, a Novel Intellectual Developmental Disability Disorder P50HD103524 · NICHD · UNIVERSITY OF WASHINGTON · PI DANIEL DOHERTY · 2020 to 2026
$9.9MSporadic Mutations and Autism Spectrum DisordersR01MH101221 · NIMH · UNIVERSITY OF WASHINGTON · PI EICHLER, EVAN · 2013 to 2025
$9.2MDevelopmental Functional Genomics in ASD ToddlersR01MH110558 · NIMH · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI COURCHESNE, ERIC, LEWIS, NATHAN ENOCH · 2016 to 2020
$3.0M1/3 Building integrative CNS networks for genomic analysis of autismR01MH109912 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GESCHWIND, DANIEL H · 2016 to 2020
$2.6MHoward Hughes Medical InstituteNHGRI NIH HHS T32 HG000035NICHD NIH HHS P50 HD103524NIMH NIH HHS R01 MH101221NIMH NIH HHS R01 MH109912NIMH NIH HHS R01 MH110558
Abstract
Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E-06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E-07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype-genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.
Indexed as
Genetic Predisposition to DiseaseBasic Helix-Loop-Helix ProteinsCase-Control StudiesCCCTC-Binding FactorCohort StudiesDNA-Binding ProteinsDNA Mutational AnalysisFemaleGenetic Association StudiesHeterogeneous-Nuclear Ribonucleoprotein UHigh-Throughput Nucleotide SequencingHumansKCNQ3 Potassium ChannelMaleMutationNeurodevelopmental DisordersBasic Helix-Loop-Helix ProteinsCCCTC-Binding FactorCTCF protein, humanDNA-Binding ProteinsHeterogeneous-Nuclear Ribonucleoprotein UHNRNPU protein, humanKCNQ3 Potassium ChannelKCNQ3 protein, humanLEO1 protein, humanRepressor ProteinsRNA-Binding ProteinsSPEN protein, humanTCF12 protein, humanTranscription FactorsZBTB18 protein, human
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