Dataset Information

Phenotypic Impact of Rare Potentially Damaging Copy Number Variation in Obsessive-Compulsive Disorder and Chronic Tic Disorders.

ABSTRACT:

Background

Recent studies report an important-and previously underestimated-role of rare variation in risk of obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD). Using data from a large epidemiological study, we evaluate the distribution of potentially damaging copy number variation (pdCNV) in OCD and CTD, examining associations between pdCNV and the phenotypes of probands, including a consideration of early- vs. late-diagnoses.

Method

The Obsessive-Compulsive Inventory-Revised (OCI-R) questionnaire was used to ascertain psychometric profiles of OCD probands. CNV were identified genome-wide using chromosomal microarray data.

Results

For 993 OCD cases, 86 (9%) were identified as pdCNV carriers. The most frequent pdCNV found was at the 16p13.11 region. There was no significant association between pdCNV and the OCI-R total score. However, pdCNV was associated with Obsessing and Checking subscores. There was no significant difference in pdCNV frequency between early- vs. late-diagnosed OCD probands. Of the 217 CTD cases, 18 (8%) were identified as pdCNV carriers. CTD probands with pdCNV were significantly more likely to have co-occurring autism spectrum disorder (ASD).

Conclusions

pdCNV represents part of the risk architecture for OCD and CTD. If replicated, our findings suggest pdCNV impact some OCD symptoms. Genes within the 16p13.11 region are potential OCD risk genes.

SUBMITTER: Mahjani B

PROVIDER: S-EPMC9601402 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Phenotypic Impact of Rare Potentially Damaging Copy Number Variation in Obsessive-Compulsive Disorder and Chronic Tic Disorders.

Mahjani Behrang B Birnbaum Rebecca R Buxbaum Grice Ariela A Cappi Carolina C Jung Seulgi S Avila Marina Natividad MN Reichenberg Abraham A Sandin Sven S Hultman Christina M CM Buxbaum Joseph D JD Grice Dorothy E DE

Genes 20221005 10

<h4>Background</h4>Recent studies report an important-and previously underestimated-role of rare variation in risk of obsessive-compulsive disorder (OCD) and chronic tic disorders (CTD). Using data from a large epidemiological study, we evaluate the distribution of potentially damaging copy number variation (pdCNV) in OCD and CTD, examining associations between pdCNV and the phenotypes of probands, including a consideration of early- vs. late-diagnoses.<h4>Method</h4>The Obsessive-Compulsive Inv ...[more]

PMID: 36292681

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Project description:Objective Patients with tic disorders (TDs) usually also have obsessive–compulsive disorder (OCD). The severity of obsessive–compulsive symptoms (OCSs) in TD is widely evaluated using the Children’s Yale–Brown Obsessive–Compulsive Scale (CY-BOCS). However, there is no survey on the severity of OCSs in patients with TD based on a Chinese sample, and the reliability and validity of the CY-BOCS in patients with TD have not been well established in China. This study examined the severity of OCSs in TDs and the psychometric properties of the CY-BOCS in Chinese pediatric patients with TD. Methods A total of 367 patients who were diagnosed with TD [152 with Tourette syndrome (TS)] were enrolled in the Department of Psychiatry at Beijing Children’s Hospital in China. The mean age of the patients was 9.21 ± 2.06 years (range: 5–16 years). The Yale Global Tic Severity Scale (YGTSS) and CY-BOCS were used as screening tools. The psychometric properties of the CY-BOCS were assessed using Cronbach’s alpha, test-retest reliability, and construct validity. Results The OCSs in TDs were 3.93 ± 5.15 based on the CY-BOCS in the whole sample. The older adolescent group showed higher scores than the young adolescent groups (Z = −3.37, p = 0.001). However, the young adolescent group showed a higher incidence rate of OCSs than the older adolescent group (p < 0.01). Men with TDs also showed a higher incidence rate of OCSs than women (p = 0.03). The reliability and validity analyses of the CY-BOCS showed Cronbach’s alpha and test-retest reliability values of 0.81 and 0.82, respectively. The CY-BOCS showed an acceptable level in the two-factor structure (obsession and compulsive) in patients with TD. The comparative fit index (CFI) was 0.84 for TD, 0.86 for Tourette, 0.94 for the younger adolescent group, and 0.74 for the older adolescent group. Conclusion More OCSs were identified in the TS group and the older adolescent group with TDs. The CY-BOCS showed good psychometric properties in children and adolescents with TD, especially in younger patients with TD. OCSs might be associated with age and functional impairment of TD.

Project description:BackgroundThe Autism Sequencing Consortium identified 102 high-confidence autism spectrum disorder (ASD) genes, showing that individuals with ASD and with potentially damaging single nucleotide variation (pdSNV) in these genes had lower cognitive levels and delayed age at walking, when compared to ASD participants without pdSNV. Here, we made use of a Swedish sample of individuals with ASD (called PAGES, for Population-Based Autism Genetics & Environment Study) to evaluate the frequency of pdSNV and their impact on medical and psychiatric phenotypes, using an epidemiological frame and universal health reporting. We then combine findings with those for potentially damaging copy number variation (pdCNV).MethodsSNV and CNV calls were generated from whole-exome sequencing and chromosome microarray data, respectively. Birth and medical register data were used to collect phenotypes.ResultsOf 808 individuals assessed by sequencing, 69 (9%) had pdSNV in the 102 ASC genes, and 144 (18%) had pdSNV in the 102 ASC genes or in a larger set of curated neurodevelopmental genes (from the Deciphering Developmental Disorders study, the gene2phenotype database, and the Radboud University gene lists). Three or more individuals had pdSNV in GRIN2B, POGZ, SATB1, DYNC1H1, SCN8A, or CREBBP. In comparison, out of the 996 individuals from whom CNV were called, 105 (11%) carried one or more pdCNV, including four or more individuals with CNV in the recurrent 15q11q13, 22q11.2, and 16p11.2 loci. Carriers of pdSNV were more likely to have intellectual disability (ID) and epilepsy, while carriers of pdCNV showed increased rates of congenital anomalies and scholastic skill disorders. Carriers of either pdSNV or pdCNV were more likely to have ID, scholastic skill disorders, and epilepsy.LimitationsThe cohort only included individuals with autistic disorder, the more severe form of ASD, and phenotypes are defined from medical registers. Not all genes studied are definitively ASD genes, and we did not have de novo information to aid in classification.ConclusionsIn this epidemiological sample, rare pdSNV were more common than pdCNV and the combined yield of potentially damaging variation was substantial at 27%. The results provide compelling rationale for the use of high-throughout sequencing as part of routine clinical workup for ASD and support the development of precision medicine in ASD.

Dataset Information

Phenotypic Impact of Rare Potentially Damaging Copy Number Variation in Obsessive-Compulsive Disorder and Chronic Tic Disorders.

Background

Method

Results

Conclusions

Publications

Phenotypic Impact of Rare Potentially Damaging Copy Number Variation in Obsessive-Compulsive Disorder and Chronic Tic Disorders.

Similar Datasets

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