Characterizing Rare DNA Copy-Number Variants in Pediatric Obsessive-Compulsive Disorder

Area of Science:

• Genetics
• Neuropsychiatry
• Developmental Biology

Background:

• Pediatric obsessive-compulsive disorder (OCD) is a common neuropsychiatric condition with a significant genetic component.
• Previous research identified rare de novo single-nucleotide variants in individuals with OCD.
• Larger studies have investigated copy-number variants (CNVs) using microarray data in OCD.

Purpose of the Study:

• To investigate the role of rare de novo CNVs in pediatric OCD using whole-exome sequencing (WES) data.
• To provide additional insight into the genetic factors and biological processes underlying OCD.
• To compare the frequency of rare de novo CNVs in individuals with OCD versus control families.

Main Methods:

• Whole-exome DNA sequencing (WES) data from 183 OCD trio families and 771 control families were analyzed.
• CNVs were detected using the eXome-Hidden Markov Model (XHMM) algorithm.
• Burden analyses and Gene Ontology enrichment analyses were performed; GATK-gCNV was used for confirmation.

Main Results:

• A significantly higher rate of rare de novo CNVs was detected in individuals with OCD (0.07 per proband) compared to controls (0.005) (rate ratio = 11.7, p = 4.00×10^-6).
• This enrichment was confirmed using the GATK-gCNV algorithm.
• Most identified rare de novo CNVs in OCD probands were predicted to be pathogenic or likely pathogenic, with enrichment in several Gene Ontology sets.

Conclusions:

• This study provides the first evidence for an enrichment of rare de novo CNVs detected by WES in pediatric OCD.
• Findings complement previous CNV studies and enhance understanding of genetic factors contributing to OCD risk.
• The results highlight the importance of de novo CNVs in the genetic architecture of OCD.