Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation
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Obsessive-compulsive disorder (OCD) is a heterogeneous neuropsychiatric condition, thought to have a significant genetic component. When onset occurs in childhood, affected individuals generally exhibit different characteristics from adult-onset OCD, including higher prevalence in males and increased heritability. Since neuropsychiatric conditions are associated with copy number variations (CNVs), we considered their potential role in the etiology of OCD. We genotyped 307 unrelated pediatric probands with idiopathic OCD (including 174 that were part of complete parent-child trios) and compared their genotypes with those of 3861 population controls, to identify rare CNVs (<0.5 % frequency) of at least 15 kb in size that might contribute to OCD. We uncovered de novo CNVs in 4/174 probands (2.3 %). Our case cohort was enriched for CNVs in genes that encode targets of the fragile X mental retardation protein (nominal p = 1.85 × 10 −03 ; FDR=0.09), similar to previous findings in autism and schizophrenia. These results also identified deletions or duplications of exons in genes involved in neuronal migration ( ASTN2 ), synapse formation ( NLGN1 and PTPRD ), and postsynaptic scaffolding ( DLGAP1 and DLGAP2 ), which may be relevant to the pathogenesis of OCD. Four cases had CNVs involving known genomic disorder loci (1q21.1-21.2, 15q11.2-q13.1, 16p13.11, and 17p12). Further, we identified BTBD9 as a candidate gene for OCD. We also sequenced exomes of ten “CNV positive” trios and identified in one an additional plausibly relevant mutation: a 13 bp exonic deletion in DRD4 . Our findings suggest that rare CNVs may contribute to the etiology of OCD.
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Both genetic and environmental factors contribute to the risk of developing OCD.
“However, both genetic and environmental factors contribute to risk of developing OCD (11–17).”
From Maternal Effects as Causes of Risk for Obsessive-Compulsive Disorder (2020) · cites this paper as [14]
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- Authors
- Gazzellone, M. J., Zarrei, M., Burton, C. L., Walker, S., Uddin, M., Shaheen, S. M., Coste, J., Rajendram, R., Schachter, R. J., Colasanto, M., Hanna, G. L., Rosenberg, D. R., Soreni, N., Fitzgerald, K. D., Marshall, C. R., Buchanan, J. A., Merico, D., Arnold, P. D., & Scherer, S. W.
- Affiliations
- Hospital for Sick Children (CA)
- University of Calgary (CA)
- University of Toronto (CA)
- University of Michigan (US)
- Wayne State University (US)
- St. Joseph’s Healthcare Hamilton (CA)
- Corresponding author
- Arnold, Paul D.
- Scherer, Stephen W.
- ORCID
- Venue
- Journal of Neurodevelopmental Disorders
- Published
- 2016-10-18
- Volume
- 8
- Issue
- 1
- Pages
- 36-36
- ISSN
- 1866-1947 (ISSN-L)
- 1866-1955
- PMC
- PMC5070001
- OpenAlex
- W2537126451
- Cited by
- 77
- References
- 64
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 9 · 2023: 8 · 2022: 7 · 2021: 8 · 2020: 8 · 2019: 11 · 2018: 7 · 2017: 9
- FWCI
- 12.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Neurodevelopmental Disorders (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- TSpace (University of Toronto) (submittedVersion, cc-by)
- Funders
- Genome Canada
- Canada Foundation for Innovation
- Canadian Institute for Advanced Research
- Government of Ontario
- Canadian Institutes of Health Research
- The Hospital for Sick Children
- University of Toronto McLaughlin centre
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- obsessive-compulsive disorder, copy number variation, pediatric OCD, de novo CNVs, rare variants, FMRP, BTBD9, DRD4, exome sequencing, genetic etiology
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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