OCD Isn't Just Psychological: Study Points To Genetic Origin Of Disorder

Obsessive-compulsive disorder (OCD) is a common mental health problem in children, in which genetic factors play a role. A recent study found that children with OCD have more rare DNA changes, called de novo CNVs, than children without the disorder. These DNA changes may affect brain function and help explain why OCD occurs. This finding reinforces the idea that OCD has a genetic origin and may help in the future to develop new treatments.

Obsessive-compulsive disorder (OCD) is a mental health problem that affects many children and adolescents. It is characterized by repetitive, unwanted thoughts (obsessions) and by behaviors or rituals that the person feels they need to do to relieve the anxiety caused by these thoughts (compulsions).

OCD is a disorder of the brain and behavior, and we know that genetic factors, that is, information that we inherit from our parents, play an important role in the development of this condition. Therefore, scientists around the world have been studying the genes of people with obsessive-compulsive disorder to better understand its causes and, who knows, help develop new treatments in the future.

The study in question, conducted by researchers at Yale University, USA, investigated a very specific part of the genes of children with obsessive-compulsive disorder.

The researchers wanted to find out whether certain rare types of genetic changes, called rare 'de novo' CNVs, appear more frequently in children with obsessive-compulsive disorder than in children without the disorder.

CNV stands for Copy Number Variation. This means that, instead of having exactly two copies of a piece of DNA (one from the father and one from the mother), the child may have more or fewer copies of certain sections.

When these changes appear out of nowhere, without being present in the parents, they are called 'de novo'. These changes can affect the functioning of genes and, in some cases, increase the risk of developing disorders such as OCD.

To conduct this research, the scientists analyzed the DNA of 183 families in which a child had OCD and 771 families in which the children did not have OCD (the controls).

They used a technology called whole exome sequencing (WES), which closely examines only the parts of the DNA that contain the genes that actually make proteins, as if focusing on the “master recipes” in a great cookbook.

Using specialized computer programs, the scientists identified these rare CNVs de novo in the children’s genetic material and compared the results between the two groups.

What they found was surprising: children with OCD had a much higher number of these rare genetic alterations than children without OCD.

To give you an idea, while controls showed an average of 0.005 CNVs per child, participants with OCD had 0.07 CNVs per child, which means a difference more than 11 times greater.

In addition, most of these alterations found in children with OCD were considered pathogenic (capable of causing disease) or likely pathogenic. When scientists analyzed the affected genes, they realized that many of them are related to important biological processes in the functioning of the brain.

In conclusion, this study was the first to show that rare de novo CNVs detected by this advanced technique (WES) are more present in children with obsessive-compulsive disorder, reinforcing the idea that OCD has an important genetic component.

This complements previous research and helps to better understand the genetic mechanisms that increase the risk of developing the disorder. These findings are an important step towards thinking about more personalized forms of prevention and treatment for obsessive-compulsive disorder in the future.

READ MORE:

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

Sarah B. Abdallah, Emily Olfson, Carolina Cappi, Samantha Greenspun, Gwyneth Zai,  Maria C. Rosário, A Jeremy Willsey, Roseli G. Shavitt, Euripedes C. Miguel, James L. Kennedy, Margaret A. Richter, and Thomas V. Fernandez

Journal of the American Academy of Child & Adolescent Psychiatry, March 20, 2025

DOI: 10.1016/j.jaac.2025.03.014 

Abstract: 

Pediatric obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder in which genetic factors play an important role. Recent studies have demonstrated an enrichment of rare de novo DNA single-nucleotide variants in persons with OCD compared to controls, and larger studies have examined copy-number variants (CNVs) using microarray data. Our study examines rare de novo CNVs using whole-exome sequencing (WES) data to provide additional insight into genetic factors and biological processes underlying OCD. We detected CNVs using whole-exome DNA sequencing (WES) data from 183 OCD trio families (unaffected parents and children with OCD) and 771 control families to test the hypothesis that rare de novo CNVs are enriched in persons with OCD compared to controls. Our primary analysis used the eXome-Hidden Markov Model (XHMM) to identify CNVs in silico. We performed burden analyses comparing persons with OCD vs controls and downstream biological systems analyses of CNVs in probands with OCD. We then used a second algorithm (GATK-gCNV) to confirm our primary analysis. Our findings demonstrate a higher rate of rare de novo CNVs detected by WES in persons with OCD (0.07 CNVs per proband) compared to controls (0.005) (corrected rate ratio = 11.7 95% CI = 3.6-50.0, p = 4.00×10-6). We confirmed this enrichment using GATK-gCNV. The majority of these rare de novo CNVs in persons with OCD are predicted to be pathogenic or likely pathogenic, and an examination of genes disrupted by rare de novo CNVs in persons with OCD finds enrichment of several Gene Ontology sets. This study shows for the first time an enrichment of rare de novo CNVs detected by WES in OCD, complementing previous, larger CNV studies and providing additional insight into genetic factors underlying OCD risk.