Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE76438 | GEO | 2016/12/11
SECONDARY ACCESSION(S): PRJNA307318
REPOSITORIES: GEO
Similar Datasets
Project description:The Affymetrix CytoScan HD 2.5M and Illumina HumanOmni2.5 arrays are high resolution SNP platform for studying copy number variations in the human genome. Both platforms have widely being used in both clinical and research settings for identifying causative variants as well as interrogating the genome for benign variants. We employed both platforms to investigate the risk factor CNVs in trios diagnosed with OCD. We genotyped 307 unrelated probands (including 174 complete parent-child trios; mean age of probands 7.9±3.5 years) and compared their genotypes to those of 3,861 population controls, in order to identify rare CNVs (<0.5% frequency) of at least 15 kb in size that might contribute to OCD. We uncovered de novo CNVs and Decipher Syndromes in probands. We have identified additional potentially risk factor CNVs impacting the coding sequencing of genes involved in brain functions.
2016-12-11 | GSE76437 | GEO
Project description:The Affymetrix CytoScan HD 2.5M and Illumina HumanOmni2.5 arrays are high resolution SNP platform for studying copy number variations in the human genome. Both platforms have widely being used in both clinical and research settings for identifying causative variants as well as interrogating the genome for benign variants. We employed both platforms to investigate the risk factor CNVs in trios diagnosed with OCD. We genotyped 307 unrelated probands (including 174 complete parent-child trios; mean age of probands 7.9±3.5 years) and compared their genotypes to those of 3,861 population controls, in order to identify rare CNVs (<0.5% frequency) of at least 15 kb in size that might contribute to OCD. We uncovered de novo CNVs and Decipher Syndromes in probands. We have identified additional potentially risk factor CNVs impacting the coding sequencing of genes involved in brain functions.
2016-12-11 | GSE76436 | GEO
Project description:Uncovering obsessive-compulsive disorder risk genes in a pediatric cohort by high-resolution analysis of copy number variation.
| PRJNA307318 | ENA
Project description:OBJECTIVE:Obsessive-compulsive disorder (OCD) and Tourette syndrome (TS) are heritable neurodevelopmental disorders with a partially shared genetic etiology. This study represents the first genome-wide investigation of large (>500 kb), rare (<1%) copy number variants (CNVs) in OCD and the largest genome-wide CNV analysis in TS to date. METHOD:The primary analyses used a cross-disorder design for 2,699 case patients (1,613 ascertained for OCD, 1,086 ascertained for TS) and 1,789 controls. Parental data facilitated a de novo analysis in 348 OCD trios. RESULTS:Although no global CNV burden was detected in the cross-disorder analysis or in secondary, disease-specific analyses, there was a 3.3-fold increased burden of large deletions previously associated with other neurodevelopmental disorders (p = .09). Half of these neurodevelopmental deletions were located in a single locus, 16p13.11 (5 case patient deletions: 0 control deletions, p = .08 in the current study, p = .025 compared to published controls). Three 16p13.11 deletions were confirmed de novo, providing further support for the etiological significance of this region. The overall OCD de novo rate was 1.4%, which is intermediate between published rates in controls (0.7%) and in individuals with autism or schizophrenia (2-4%). CONCLUSION:Several converging lines of evidence implicate 16p13.11 deletions in OCD, with weaker evidence for a role in TS. The trend toward increased overall neurodevelopmental CNV burden in TS and OCD suggests that deletions previously associated with other neurodevelopmental disorders may also contribute to these phenotypes.
| S-EPMC4218748 | biostudies-literature
Project description:Obsessive-compulsive disorder (OCD) is a prevalent and often severely disabling illness with onset generally in childhood or adolescence. Although white matter deficits have been implicated in the neurobiology of OCD, few studies have been conducted in pediatric patients when the brain is still developing and have examined their functional correlates. In this study, 23 pediatric OCD patients and 23 healthy volunteers, between the ages of 9 and 17 years, matched for sex, age, handedness, and IQ, received a diffusion tensor imaging exam on a 3T GE system and a brief neuropsychological battery tapping executive functions. Patient symptom severity was assessed using the Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). Patients with OCD exhibited significantly greater fractional anisotropy compared to matched controls in the left dorsal cingulum bundle, splenium of the corpus callosum, right corticospinal tract, and left inferior fronto-occipital fasciculus. There were no regions of significantly lower fractional anisotropy in patients compared to controls. Higher fractional anisotropy in the splenium was significantly correlated with greater obsession severity on the CY-BOCS in the subgroup of psychotropic drug-naïve patients. Among patients, there was a significant association between greater fractional anisotropy in the dorsal cingulum bundle and better performance on measures of response inhibition and cognitive control. The overall findings suggest a pattern of greater directional coherence of white matter tracts in OCD very early in the course of illness, which may serve a compensatory mechanism, at least for response inhibition functions typically subserved by the cingulum bundle.
| S-EPMC3473339 | biostudies-other
Project description:OBJECTIVE:To review progress in understanding pediatric obsessive-compulsive disorder (OCD). The focus is on the frontal-striatal-thalamic model of OCD, neurobiological and genetic studies of the disorder, and their influence on recent advances in treatment. METHOD:Computerized literature searches were conducted with the key words "obsessive-compulsive disorder" in conjunction with "pediatric," "genetics," and "imaging." RESULTS:Neuroimaging studies find evidence to support the frontal-striatal-thalamic model. Genetic and neurochemical studies also implicate glutamate in the pathological finding of OCD. This has led to the application of glutamate-modulating agents to treat OCD. CONCLUSIONS:Studies of pediatric OCD have led to a refined frontal-striatal-thalamic model of pathogenesis and are having an evidence-based impact on treatment. Despite this progress, fully explanatory models are still needed that would allow for accurate prognosis and the development of targeted and efficacious treatments.
| S-EPMC2696312 | biostudies-literature
Project description:OBJECTIVE:Brain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken. METHOD:T1-weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume. RESULTS:In adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from -0.10 to -0.33. CONCLUSIONS:The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.
| S-EPMC7106947 | biostudies-literature
Project description:BACKGROUND:The brain mechanisms of cognitive-behavioral therapy (CBT), a highly effective treatment for pediatric obsessive-compulsive disorder (OCD), are unknown. Neuroimaging in adult OCD indicates that CBT is associated with metabolic changes in striatum, thalamus, and anterior cingulate cortex. We therefore probed putative metabolic effects of CBT on these brain structures in pediatric OCD using proton magnetic resonance spectroscopic imaging (1H MRSI). METHOD:Five unmedicated OCD patients (4 ♀, 13.5±2.8) and 9 healthy controls (7 ♀, 13.0±2.5) underwent MRSI (1.5 T, repetition-time/echo-time=1500/30 ms) of bilateral putamen, thalamus and pregenual anterior cingulate cortex (pACC). Patients were rescanned after 12 weeks of exposure-based CBT. The Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) of OCD symptoms was administered before and after CBT. RESULTS:Four of 5 patients responded to CBT (mean 32.8% CY-BOCS reduction). Multiple metabolite effects emerged. Pre-CBT, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate (tNAA) in left pregenual anterior cingulate cortex (pACC) was 55.5% higher in patients than controls. Post-CBT, tNAA (15.0%) and Cr (23.9%) in left pACC decreased and choline compounds (Cho) in right thalamus increased (10.6%) in all 5 patients. In left thalamus, lower pre-CBT tNAA, glutamate+glutamine (Glx), and myo-inositol (mI) predicted greater post-CBT drop in CY-BOCS (r=0.98) and CY-BOCS decrease correlated with increased Cho. CONCLUSIONS:Interpretations are offered in terms of the Glutamatergic Hypothesis of Pediatric OCD. Similar to 18FDG-PET in adults, objectively measurable regional MRSI metabolites may indicate pediatric OCD and predict its response to CBT.
| S-EPMC4344316 | biostudies-other
Project description:Neurogenetics of Obsessive-Compulsive Disorder
| PRJNA588485 | ENA
Project description:Neurogenetics of Obsessive-Compulsive Disorder
| PRJNA588486 | ENA