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, 10 (1), 68

High Resolution Chromosomal Microarray Analysis in Paediatric Obsessive-Compulsive Disorder


High Resolution Chromosomal Microarray Analysis in Paediatric Obsessive-Compulsive Disorder

Edna Grünblatt et al. BMC Med Genomics.


Background: Obsessive-Compulsive Disorder (OCD) is a common and chronic disorder in which a person has uncontrollable, reoccurring thoughts and behaviours. It is a complex genetic condition and, in case of early onset (EO), the patients manifest a more severe phenotype, and an increased heritability. Large (>500 kb) copy number variations (CNVs) previously associated with autism and schizophrenia have been reported in OCD. Recently, rare CNVs smaller than 500 kb overlapping risk loci for other neurodevelopmental conditions have also been reported in OCD, stressing the importance of examining CNVs of any size range. The aim of this study was to further investigate the role of rare and small CNVs in the aetiology of EO-OCD.

Methods: We performed high-resolution chromosomal microarray analysis in 121 paediatric OCD patients and in 124 random controls to identify rare CNVs (>50 kb) which might contribute to EO-OCD.

Results: The frequencies and the size of the observed rare CNVs in the patients did not differ from the controls. However, we observed a significantly higher frequency of rare CNVs affecting brain related genes, especially deletions, in the patients (OR = 1.98, 95% CI 1.02-3.84; OR = 3.61, 95% CI 1.14-11.41, respectively). Similarly, enrichment-analysis of CNVs gene content, performed with three independent methods, confirmed significant clustering of predefined genes involved in synaptic/brain related functional pathways in the patients but not in the controls. In two patients we detected de-novo CNVs encompassing genes previously associated with different neurodevelopmental disorders (NRXN1, ANKS1B, UHRF1BP1).

Conclusions: Our results further strengthen the role of small rare CNVs, particularly deletions, as susceptibility factors for paediatric OCD.

Keywords: CNV; De-novo; Early-onset; Enrichment analysis; OCD.

Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the respective local ethics committees with the latest version of the Declaration of Helsinki, including an ethical permission granted by the Ethic Committees from Würzburg and the Cantonal Ethic Commission of Zürich (Ref. Nr. 39/97, 140/3 and EK: KEK-ZH-Nr. 2010–0340/3) and written informed consent was obtained in all cases from the participants or/and their parents.

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests. SW has received lecture honoraria from Eli-Lily, Opopharma in the last 5 years. Outside professional activities and interests are declared, for AR and SW, under the link of the University of Zurich However, the above did not affect the reporting in the current work.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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