TY  - JOUR
A1  - Franke, Maximilian
A1  - Conzelmann, Annette
A1  - Grünblatt, Edna
A1  - Werling, Anna M.
A1  - Spieles, Helen
A1  - Wewetzer, Christoph
A1  - Warnke, Andreas
A1  - Romanos, Marcel
A1  - Walitza, Susanne
A1  - Renner, Tobias J.
T1  - No Association of Variants of the NPY-System With Obsessive-Compulsive Disorder in Children and Adolescents
JF  - Frontiers in Molecular Neuroscience
N2  - Obsessive-compulsive disorder (OCD) causes severe distress and is therefore counted by the World Health Organisation (WHO) as one of the 10 most impairing illnesses. There is evidence for a strong genetic underpinning especially in early onset OCD (eoOCD). Though several genes involved in neurotransmission have been reported as candidates, there is still a need to identify new pathways. In this study, we focussed on genetic variants of the Neuropeptide Y (NPY) system. NPY is one of the most abundant neuropeptides in the human brain with emerging evidence of capacity to modulate stress response, which is of high relevance in OCD. We focussed on tag-SNPs of NPY and its receptor gene NPY1R in a family-based approach. The sample comprised 86 patients (children and adolescents) with eoOCD with both their biological parents. However, this first study on genetic variants of the NPY-system could not confirm the association between the investigated SNPs and eoOCD. Based on the small sample size results have to be interpreted as preliminary and should be replicated in larger samples. However, also in an additional GWAS analysis in a large sample, we could not observe an associations between NPY and OCD. Overall, these preliminary results point to a minor role of NPY on the stress response of OCD.
KW  - NPY
KW  - obsessive-compulsive
KW  - children
KW  - anxiety
KW  - neuropeptide
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229051
VL  - 12
ER  - 
TY  - JOUR
A1  - Grünblatt, Edna
A1  - Oneda, Beatrice
A1  - Ekici, Arif B.
A1  - Ball, Juliane
A1  - Geissler, Julia
A1  - Uebe, Steffen
A1  - Romanos, Marcel
A1  - Rauch, Anita
A1  - Walitza, Susanne
T1  - High resolution chromosomal microarray analysis in paediatric obsessive-compulsive disorder
JF  - BMC Medical Genomics
N2  - 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 \(\textit{NRXN1, ANKS1B, UHRF1BP1}\)).

Conclusions
Our results further strengthen the role of small rare CNVs, particularly deletions, as susceptibility factors for paediatric OCD.
KW  - Medicine
KW  - OCD
KW  - CNV
KW  - Enrichment analysis
KW  - De-novo
KW  - Early-onset
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172791
VL  - 10
IS  - 68
ER  -