{
  "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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Psychiatry and Behavioral Sciences, UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA USA",
    "Department of Neuroscience, Yale School of Medicine, New Haven, CT USA",
    "Child Study Center, Yale University School of Medicine, New Haven, CT USA",
    "Department of Microbiology, Immunology, and Molecular Genetics, University of California Los Angeles, Los Angeles, CA USA",
    "Department of Psychiatry, University of Rochester, Rochester, NY USA",
    "Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers, the State University of New Jersey, Piscataway, NJ USA",
    "Center for OCD, Anxiety and Related Disorders, University of Florida, Gainesville, FL USA",
    "Department of Psychology, University of California, Los Angeles, CA USA",
    "Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL USA",
    "OCD Institute, McLean Hospital, Belmont, MA USA",
    "Department of Psychiatry, Harvard Medical School, Boston, MA USA",
    "Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA USA",
    "Rogers Behavioral Health, Philadelphia, PA USA",
    "Private practice, San Jose, Costa Rica",
    "Department of Psychiatry and Behavioral Sciences, Child and Adolescent Psychiatry, Johns Hopkins University, Baltimore, MD USA",
    "Department of Psychiatry and Human Behavior, Thomas Jefferson University Hospital, Philadelphia, PA USA",
    "Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX USA",
    "Departamento de Psiquiatria, Faculdade de Medicina, Universidade de São Paulo, Sao Paulo, Brazil",
    "Department of Genetics and the Human Genetics Institute of New Jersey, Rutgers, the State University of New Jersey, Piscataway, NJ USA",
    "Asociación de Psiquiatras de Argentina, Buenos Aires, Argentina",
    "Department of Psychiatry, Yale University School of Medicine, New Haven, CT USA",
    "Department of Neuroscience, Yale University School of Medicine, New Haven, CT USA",
    "Department of Psychology, Yale University Graduate School of Arts and Sciences, New Haven, CT USA",
    "Center for Brain and Mind Health, Yale University School of Medicine, New Haven, CT USA",
    "Wu-Tsai Institute, Yale University, New Haven, CT USA",
    "Department of Psychiatry, Columbia University, New York, NY USA",
    "Center for OCD and Related Disorders, New York State Psychiatric Institute, New York, NY USA",
    "UF Health Rehab Center, Norman Fixel Institute for Neurological Diseases, University of Florida, Gainesville, FL USA",
    "Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey, Piscataway, NJ USA",
    "Child Health Institute of New Jersey, Robert Wood Johnson Medical School, New Brunswick, NJ USA",
    "Department of Psychiatry, University of California, San Diego, CA USA",
    "University Hospital of Psychiatry Zurich, Child and Adolescent Psychiatry and Psychotherapy, Zurich, Switzerland",
    "Department of Child Psychiatry, Feinberg Child Study Center, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel",
    "Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel",
    "Department of Human Genetics, McGill University, Montreal, Québec Canada",
    "Yonsei University College of Medicine, Severance Hospital, Seoul, South Korea",
    "Department of Child and Adolescent Psychiatry, Faculty of Medicine of the TU Dresden, Dresden, Germany",
    "Clinic of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany",
    "Evelina London Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK",
    "School of Life Sciences and Medicine, King’s College London, London, UK"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 127,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Belinda Wang",
      "orcid": "0000-0001-5563-894X"
    },
    {
      "affs": [
        0
      ],
      "name": "Matthew N. Tran"
    },
    {
      "affs": [
        0
      ],
      "name": "Sheng Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Yuting Liu"
    },
    {
      "affs": [
        2
      ],
      "name": "Emily Olfson"
    },
    {
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        0
      ],
      "name": "George Wang",
      "orcid": "0009-0005-7879-3519"
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    {
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        0
      ],
      "name": "Nawei Sun",
      "orcid": "0000-0002-1599-5990"
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        0
      ],
      "name": "Jeanselle Dea",
      "orcid": "0000-0003-3831-3558"
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        3
      ],
      "name": "Charles Ochieng’ Olwal"
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        4
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      "name": "Lyvia Bertolace"
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        2
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      "name": "Michael H. Bloch",
      "orcid": "0000-0003-0352-4080"
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        5
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      "name": "Carolina Cappi"
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        6
      ],
      "name": "Yi-Chieh Chang"
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        7
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      "name": "Denise Chavira"
    },
    {
      "affs": [
        8
      ],
      "name": "Barbara J. Coffey"
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        9,
        10
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      "name": "Martha J. Falkenstein"
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        11
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      "name": "Adam C. Frank"
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        12
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      "name": "Martin E. Franklin"
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        6
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      "name": "Stephanie Garayalde"
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        13
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        14
      ],
      "name": "Marco Grados"
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        15
      ],
      "name": "Rami Hatem"
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        9
      ],
      "name": "Allyna-London Howell"
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        0
      ],
      "name": "Starlette Khim"
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        9,
        10
      ],
      "name": "Jennie M. Kuckertz",
      "orcid": "0000-0002-3929-2683"
    },
    {
      "affs": [
        6
      ],
      "name": "Mindy M. Le"
    },
    {
      "affs": [
        0
      ],
      "name": "Allison Libby"
    },
    {
      "affs": [
        16
      ],
      "name": "Ryan J. McCarty"
    },
    {
      "affs": [
        9,
        10
      ],
      "name": "Mary E. McNamara"
    },
    {
      "affs": [
        6
      ],
      "name": "Daniel McNeil"
    },
    {
      "affs": [
        17
      ],
      "name": "Euripedes C. Miguel",
      "orcid": "0000-0002-9393-3103"
    },
    {
      "affs": [
        18
      ],
      "name": "Cara Nasello"
    },
    {
      "affs": [
        6
      ],
      "name": "Binh Nguyen"
    },
    {
      "affs": [
        0
      ],
      "name": "Tenzin Norbu"
    },
    {
      "affs": [
        9
      ],
      "name": "Lauren Oh"
    },
    {
      "affs": [
        6
      ],
      "name": "Ashley Ordway"
    },
    {
      "affs": [
        6
      ],
      "name": "Catherine Paciotti"
    },
    {
      "affs": [
        19
      ],
      "name": "Viviana A. Peskin"
    },
    {
      "affs": [
        2,
        20,
        21,
        22,
        23,
        24
      ],
      "name": "Christopher Pittenger",
      "orcid": "0000-0003-2117-9321"
    },
    {
      "affs": [
        25,
        26
      ],
      "name": "Helen Blair Simpson"
    },
    {
      "affs": [
        27
      ],
      "name": "Heather Simpson Martin"
    },
    {
      "affs": [
        28,
        29
      ],
      "name": "Max A. Tischfield"
    },
    {
      "affs": [
        18
      ],
      "name": "Jinchuan Xing",
      "orcid": "0000-0001-6469-8733"
    },
    {
      "affs": [
        30
      ],
      "name": "Jessica J. Zakrzewski",
      "orcid": "0000-0002-6821-2603"
    },
    {
      "name": "Belinda Wang"
    },
    {
      "affs": [
        0
      ],
      "name": "Belinda Wang",
      "orcid": "0000-0001-5563-894X"
    },
    {
      "affs": [
        0
      ],
      "name": "Sheng Wang"
    },
    {
      "affs": [
        8
      ],
      "name": "Barbara J. Coffey"
    },
    {
      "affs": [
        18
      ],
      "name": "Cara Nasello"
    },
    {
      "affs": [
        28,
        29
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      "name": "Max A. Tischfield"
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    {
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        18
      ],
      "name": "Jinchuan Xing",
      "orcid": "0000-0001-6469-8733"
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    {
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        31
      ],
      "name": "Juliane Ball"
    },
    {
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        32,
        33
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      "name": "Noa Benaroya-Milshtein"
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    {
      "affs": [
        34
      ],
      "name": "Kate Bornais"
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    {
      "affs": [
        35
      ],
      "name": "Keun-Ah Cheon"
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    {
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        36
      ],
      "name": "Erik M. Elster"
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        32,
        33
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      "name": "Dana Feldman"
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        37
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      "name": "Carolin Fremer"
    },
    {
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        18
      ],
      "name": "Danea Glover"
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        38,
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      "name": "Tammy Hedderly"
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  "bibtex": "https://research.draconitic.com/paper/3xx6ar4j8m5gm.bib",
  "cited_by": 1,
  "doi": "10.1038/s41593-026-02419-5",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13724258/",
  "id": "3xx6ar4j8m5gm",
  "issns": [
    "1097-6256",
    "1546-1726"
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  "landing_url": "https://doi.org/10.1038/s41593-026-02419-5",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
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      "3203|Obsessive-Compulsive Spectrum Disorders"
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  "pdf_url": "https://www.nature.com/articles/s41593-026-02419-5.pdf",
  "pmcid": "PMC13724258",
  "pmid": "42680906",
  "published": "2026-09-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3xx6ar4j8m5gm.ris",
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    {
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      "native_id": "PMC13724258",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s41593-026-02419-5"
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  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:3203|Obsessive-Compulsive Spectrum Disorders",
      "subfield": "psychiatry"
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  ],
  "title": "Whole-exome sequencing in individuals with obsessive–compulsive disorder and chronic tic disorders identifies 36 large-effect risk genes",
  "title_text": "Whole-exome sequencing in individuals with obsessive–compulsive disorder and chronic tic disorders identifies 36 large-effect risk genes",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:20:48Z",
  "url": "https://research.draconitic.com/paper/3xx6ar4j8m5gm",
  "venue": "Nature Neuroscience",
  "versions": []
}