Researchers at Rutgers University have identified 36 genes that substantially increase the risk of obsessive-compulsive disorder and chronic tic disorders, according to a study published in Nature Neuroscience. The genetic analysis, led by researchers at Rutgers University, including Gary Heiman and Jay Tischfield, expands the catalog of shared risk genes from a previous total of four high-confidence genes and reveals biological connections with autism and schizophrenia.
Expanding the Genetic Catalog of OCD and Chronic Tic Disorders
Obsessive-compulsive disorder and chronic tic disorders, such as Tourette disorder, affect up to 2 percent of the population and frequently co-occur. According to the study, 50 percent of individuals with chronic tic disorders also display obsessive-compulsive behaviors, while up to 30 percent of individuals with OCD have a history of tics. Despite this high comorbidity and strong heritability, researchers previously had access to only four high-confidence risk genes.
To deepen this understanding, the research team analyzed newly and previously sequenced exome data from nearly 4,000 individuals with OCD, chronic tic disorders, or both. This cohort included over 2,400 parent-child trios and more than 1,500 singletons, nearly doubling previous sample sizes. Gary Heiman noted that samples collected by families over a 20-year period became incredibly valuable as modern genome sequencing technologies advanced.
Neural Circuits and Gene Networks Implicated in Brain Development
By comparing human, rhesus macaque, and mouse brain maps, the researchers outlined a neural blueprint for these conditions based on spatial brain regions, gene expression timelines, and affected cell types. The findings provide further evidence that these conditions are mediated by dysfunction in the cortico-striato-thalamo-cortical circuit, an expansive brain loop associated with cognition, impulse control, movement, and data processing.
Risk-associated genes showed increased expression during prenatal and postnatal stages within the cortex, striatum, and thalamus. Additional expression was detected postnatally in the cerebellum. The researchers also implicated telencephalic projecting excitatory neurons, which are vital for communication across brain regions. Jay Tischfield explained that these genes act in networks rather than individually, allowing future therapies to target entire functional networks.
Large-Effect Risk Genes and Overlap With Other Neurodevelopmental Disorders
The newly identified genes carry substantial effects, increasing risk by 57-fold on average, and up to a 210-fold increase at the extreme end. Furthermore, the analysis confirmed substantial genetic overlap between the two conditions, with 30 of the 36 identified genes associated with both OCD and chronic tic cases.
Some of these risk genes also showed associations with other neurodevelopmental disorders, including autism spectrum disorder, developmental delays, and schizophrenia. However, these genes did not show overlap with congenital heart disease, a control condition that is inheritable but independent of neural development. With the number of known large-effect risk genes increased by a factor of ten, researchers anticipate expanded opportunities for the pharmaceutical industry to develop targeted treatments.
Did You Know? Genome sequencing focuses on the exome—the DNA associated with making proteins—which comprises approximately one percent of the entire genome.
Frequently Asked Questions
What are the primary findings of the Rutgers University genetic study?
Researchers identified 36 genes that substantially increase the risk of obsessive-compulsive disorder and chronic tic disorders, expanding the previous total of four high-confidence genes.
How do OCD and chronic tic disorders relate genetically?
The study found substantial genetic overlap, noting that 30 of the 36 identified risk genes were associated with both conditions.
Which brain regions are most affected by these risk genes?
Risk-associated genes show increased expression in the cortico-striato-thalamo-cortical circuit, including the cortex, striatum, thalamus, and cerebellum.
Do these risk genes overlap with other conditions?
Yes, some of the identified risk genes are also associated with autism spectrum disorder, developmental delays, and schizophrenia.
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