ArticleNature neuroscience2026
Whole-exome sequencing in individuals with obsessive-compulsive disorder and chronic tic disorders identifies 36 large-effect risk genes.
Abstract read
In one paragraph
Article in Nature neuroscience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
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
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
65 authors.
Belinda WangDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-5563-894X
Matthew N TranDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Sheng WangDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Yuting LiuDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA.
Emily OlfsonChild Study Center, Yale University School of Medicine, New Haven, CT, USA.
George WangDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0009-0005-7879-3519
Nawei SunDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-1599-5990
Jeanselle DeaDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3831-3558
Charles Ochieng' OlwalDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, USA.
Lyvia BertolaceDepartment of Psychiatry, University of Rochester, Rochester, NY, USA.
Michael H BlochChild Study Center, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0352-4080
Carolina CappiDepartment of Psychiatry, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, Piscataway, NJ, USA.
Yi-Chieh ChangCenter for OCD, Anxiety and Related Disorders, University of Florida, Gainesville, FL, USA.
Denise ChaviraDepartment of Psychology, University of California, Los Angeles, CA, USA.
Barbara J CoffeyDepartment of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, USA.
Martha J FalkensteinOCD Institute, McLean Hospital, Belmont, MA, USA.
Adam C FrankDepartment of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Martin E FranklinRogers Behavioral Health, Philadelphia, PA, USA.
Stephanie GarayaldeCenter for OCD, Anxiety and Related Disorders, University of Florida, Gainesville, FL, USA.
Helena GarridoPrivate practice, San Jose, Costa Rica.
Marco GradosDepartment of Psychiatry and Behavioral Sciences, Child and Adolescent Psychiatry, Johns Hopkins University, Baltimore, MD, USA.
Rami HatemDepartment of Psychiatry and Human Behavior, Thomas Jefferson University Hospital, Philadelphia, PA, USA.
Allyna-London HowellOCD Institute, McLean Hospital, Belmont, MA, USA.
Starlette KhimDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Jennie M KuckertzOCD Institute, McLean Hospital, Belmont, MA, USA.ORCID http://orcid.org/0000-0002-3929-2683
Mindy M LeCenter for OCD, Anxiety and Related Disorders, University of Florida, Gainesville, FL, USA.
Allison LibbyDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Ryan J McCartyDepartment of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
Mary E McNamaraOCD Institute, McLean Hospital, Belmont, MA, USA.
Daniel McNeilCenter for OCD, Anxiety and Related Disorders, University of Florida, Gainesville, FL, USA.
Euripedes C MiguelDepartamento de Psiquiatria, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil.ORCID http://orcid.org/0000-0002-9393-3103
Cara NaselloDepartment of Genetics and the Human Genetics Institute of New Jersey, Rutgers, the State University of New Jersey, Piscataway, NJ, USA.
Binh NguyenCenter for OCD, Anxiety and Related Disorders, University of Florida, Gainesville, FL, USA.
Tenzin NorbuDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Lauren OhOCD Institute, McLean Hospital, Belmont, MA, USA.
Ashley OrdwayCenter for OCD, Anxiety and Related Disorders, University of Florida, Gainesville, FL, USA.
Catherine PaciottiCenter for OCD, Anxiety and Related Disorders, University of Florida, Gainesville, FL, USA.
Viviana A PeskinAsociación de Psiquiatras de Argentina, Buenos Aires, Argentina.
Christopher PittengerChild Study Center, Yale University School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-2117-9321
Helen Blair SimpsonDepartment of Psychiatry, Columbia University, New York, NY, USA.
Heather Simpson MartinUF Health Rehab Center, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL, USA.
Max A TischfieldDepartment of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey, Piscataway, NJ, USA.
Jinchuan XingDepartment of Genetics and the Human Genetics Institute of New Jersey, Rutgers, the State University of New Jersey, Piscataway, NJ, USA.ORCID http://orcid.org/0000-0001-6469-8733
Jessica J ZakrzewskiDepartment of Psychiatry, University of California, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-6821-2603
Tourette International Collaborative Genetics (TIC Genetics)
Andrea DietrichDepartment of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Donald L GilbertDivision of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.ORCID http://orcid.org/0000-0002-9245-6878
Pieter J HoekstraDepartment of Child and Adolescent Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0003-1018-9954
Young Shin KimDepartment of Psychiatry and Behavioral Sciences, Dell Medical School, University of Texas at Austin, Austin, TX, USA.
Samuel KupermanDepartment of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.ORCID http://orcid.org/0000-0002-5995-1981
Alyssa RosenDivision of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Samuel H ZinnerDepartment of Pediatrics, Division of Developmental Medicine, University of Washington School of Medicine, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7736-9629
Mehdi BouhaddouDepartment of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, USA.
Robert A KingChild Study Center, Yale University School of Medicine, New Haven, CT, USA.
Guy RouleauDepartment of Neurology and Neurosurgery, Montreal Neurological Institute-Hospital, McGill University, Montreal, Quebec, Canada.ORCID http://orcid.org/0000-0001-8403-1418
Kerry J ResslerOCD Institute, McLean Hospital, Belmont, MA, USA.ORCID http://orcid.org/0000-0002-5158-1103
Carol A MathewsCenter for OCD, Anxiety and Related Disorders, University of Florida, Gainesville, FL, USA.ORCID http://orcid.org/0000-0003-2208-7058
Nevan J KroganQuantitative Biosciences Institute (QBI), University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-4902-337X
Nenad SestanDepartment of Neuroscience, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0966-9619
Jay A TischfieldDepartment of Genetics and the Human Genetics Institute of New Jersey, Rutgers, the State University of New Jersey, Piscataway, NJ, USA. jay@dls.rutgers.edu.
A Moses LeeDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA. andrewmoses.lee@ucsf.edu.
Gary A HeimanDepartment of Genetics and the Human Genetics Institute of New Jersey, Rutgers, the State University of New Jersey, Piscataway, NJ, USA. heiman@rutgers.edu.ORCID http://orcid.org/0000-0001-5859-0259
Thomas V FernandezChild Study Center, Yale University School of Medicine, New Haven, CT, USA. thomas.fernandez@yale.edu.ORCID http://orcid.org/0000-0003-0830-022X
A Jeremy WillseyDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA. jeremy@willseylab.com.
Matthew W StateDepartment of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, USA. matthew.state@ucsf.edu.ORCID http://orcid.org/0000-0003-1624-8302
Funding
1/7 Collaborative Genomic Studies of Tourette Disorder.R01MH115958 · NIMH · RUTGERS, THE STATE UNIV OF N.J. · PI HEIMAN, GARY A., TISCHFIELD, JAY ARNOLD · 2018 to 2023
$6.8MTRAINING THE NEXT GENERATION OF MENTAL HEALTH RESEARCHERSR25MH060482 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI DANIEL H MATHALON, Susan M. Voglmaier · 2000 to 2026
$5.2M2/7-Collaborative genomic studies of Tourette DisorderR01MH115963 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STATE, MATTHEW W. · 2018 to 2022
$4.9MDysregulation of dopamine receptors in the basal ganglia in OCD and tic disorders: Positron Emission Tomography with [11C]-PHNOR01MH130609 · NIMH · YALE UNIVERSITY · PI Christopher John Pittenger · 2022 to 2026
$3.7MBrain Network Changes Accompanying and Predicting Responses to Pharmacotherapy in OCDR01MH116038 · NIMH · YALE UNIVERSITY · PI ANTICEVIC, ALAN, PITTENGER, CHRISTOPHER JOHN · 2019 to 2023
$3.7MNeurogenetic Investigations of Obsessive-Compulsive DisorderR01MH114927 · NIMH · YALE UNIVERSITY · PI FERNANDEZ, THOMAS V · 2018 to 2022
$2.8MLeveraging Machine Learning Approaches to Understand Mechanisms of Exposure Therapy in Real-World SettingsR01MH135899 · NIMH · SAN DIEGO STATE UNIVERSITY · PI Jennie M Kuckertz · 2024 to 2026
$2.3MNeurogenomic Investigations of Trichotillomania and Excoriation DisorderK08MH128665 · NIMH · YALE UNIVERSITY · PI Emily Hunt Olfson · 2022 to 2026
$1.0MInterpretation Bias as a Mechanism of Treatment Response in OCD - Administrative SupplementK23MH126193 · NIMH · MCLEAN HOSPITAL · PI Martha J Falkenstein · 2021 to 2026
$1.0MDirect Intracranial Electrophysiological Mapping of Insular Circuits for Anxiety in the Human BrainK23MH125018 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LEE, ANDREW MOSES · 2021 to 2025
$1.0MLINKAGE &ASSOCIATION IN OBSESSIVE-COMPULSIVE DISORDERK23MH066284 · NIMH · JOHNS HOPKINS UNIVERSITY · PI GRADOS, MARCO A · 2002 to 2006
$887k4/7-Collaborative genomic studies of Tourette DisorderR01MH115962 · NIMH · CINCINNATI CHILDRENS HOSP MED CTR · PI GILBERT, DONALD L · 2018 to 2022
$810kTourette Association of America (National Tourette Syndrome Association) Young Investigator AwardU.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) K08MH128665U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) K23MH066284U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) K23MH125018U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) K23MH126193U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) K99MH128540U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH114927U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH115958U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH115959U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH115960U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH115961U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH115962U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH115963U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH115993U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH116038U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH130609U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R01MH135899U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) R25MH060482
Abstract
Obsessive-compulsive disorder (OCD) and chronic tic disorders (CTDs) are highly heritable. Rare mutations confer large risks for OCD and CTDs but only four high-confidence (hc) genes have been identified. Here we analyzed whole-exome sequencing data from 3,964 individuals with OCD, CTDs or both, including 2,418 trios. We found an excess in cases of de novo and rare protein-damaging mutations and identified 36 hc genes (false discovery rate < 0.1), including four previously identified hc genes (CELSR3, CHD8, SCUBE1 and WWC1) and four genes that overlap with OCD genome-wide association study loci (BRWD1, CELSR3, QRICH1 and SYNE1). Risk genes are shared among OCD, CTDs and other neurodevelopmental conditions. Transcriptomic and network analyses highlight mechanistic convergence and increased risk gene expression in postnatal cerebellum, prenatal and postnatal cortex and striatum. Dozens of large-effect OCD and CTD genes offer insights into pathogenesis and a path forward for illuminating pathophysiology and identifying novel treatment targets.
Identifiers
PMID
42680906What OpenQuestion holds
Textmetadata
Read underepoch 390
Registered trials
None linked
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.