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Open Access 01-12-2016 | Research

Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation

Authors: Matthew J. Gazzellone, Mehdi Zarrei, Christie L. Burton, Susan Walker, Mohammed Uddin, S. M. Shaheen, Julie Coste, Rageen Rajendram, Reva J. Schachter, Marlena Colasanto, Gregory L. Hanna, David R. Rosenberg, Noam Soreni, Kate D. Fitzgerald, Christian R. Marshall, Janet A. Buchanan, Daniele Merico, Paul D. Arnold, Stephen W. Scherer

Published in: Journal of Neurodevelopmental Disorders | Issue 1/2016

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

Our findings suggest that rare CNVs may contribute to the etiology of OCD.

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Title: Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation
Authors: Matthew J. Gazzellone
Mehdi Zarrei
Christie L. Burton
Susan Walker
Mohammed Uddin
S. M. Shaheen
Julie Coste
Rageen Rajendram
Reva J. Schachter
Marlena Colasanto
Gregory L. Hanna
David R. Rosenberg
Noam Soreni
Kate D. Fitzgerald
Christian R. Marshall
Janet A. Buchanan
Daniele Merico
Paul D. Arnold
Stephen W. Scherer
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Journal of Neurodevelopmental Disorders / Issue 1/2016
Print ISSN: 1866-1947
Electronic ISSN: 1866-1955
DOI: https://doi.org/10.1186/s11689-016-9170-9

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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