OCD and Tourette Syndrome Share Genetic Risk Factors, Large Study Finds

Scientists have identified dozens of genes associated with substantially increased risk of obsessive-compulsive disorder and chronic tic disorders, including Tourette syndrome. The findings provide new evidence that OCD and tic disorders share aspects of their genetic architecture and involve overlapping neurodevelopmental pathways.

In a large study published in Nature Neuroscience and led by researchers at Rutgers University, scientists analyzed exome data from nearly 4,000 people with OCD, tic disorders or both. The exome comprises the protein-coding portions of DNA, representing roughly 1% of the genome while containing many variants capable of disrupting gene function.

Previously, only four genes had reached high-confidence status in relation to these conditions. The new analysis identified 36 genes associated with substantially increased risk of OCD, Tourette syndrome or related tic disorders, considerably expanding the number of implicated genes.

Shared genetic roots and brain circuits

The analysis found considerable genetic overlap between OCD and tic disorders, with 30 of the 36 identified genes implicated in both conditions. Clinical overlap between the disorders is also common: approximately half of people with chronic tic disorders display obsessive-compulsive behaviors, while up to 30% of people with OCD have a history of tics.

Researchers combined the genetic findings with brain-expression maps from humans, rhesus macaques and mice to investigate where and when the implicated genes are active.

Risk genes showed enriched expression in regions associated with cortico-striato-thalamo-cortical circuitry, which connects areas including the cortex, striatum and thalamus and has been implicated in motor, cognitive and behavioral processes relevant to OCD and tic disorders.

The researchers also identified developmental patterns in gene expression, including activity during prenatal and early postnatal periods. The cerebellum showed additional enrichment after birth, supporting the involvement of brain networks extending beyond the traditionally emphasized cortico-striatal circuitry.

These expression patterns identify potentially relevant developmental periods and brain regions, but they do not establish that altered activity in any single region directly causes OCD or tic disorders.

How the risk genes may exert their effects

The analysis highlighted telencephalic projecting excitatory neurons as one cell population enriched for expression of the implicated genes. These neurons participate in communication across brain regions and could represent one cellular context in which genetic disruptions influence neurodevelopment.

The genes also appeared within interconnected biological networks rather than functioning as a single pathway. Understanding how these networks influence neuronal development and signaling could eventually help researchers identify biological processes relevant to treatment.

However, the discovery of a risk gene does not automatically make it a viable drug target. Considerably more research is required to determine how particular variants alter cellular function and whether those changes can be safely modified therapeutically.

Some of the rare variants identified in the analysis were associated with unusually large estimated effects. Across the implicated genes, risk estimates were around 57-fold on average, with some estimates exceeding 200-fold.

These figures require careful interpretation. They refer to rare damaging variants identified through statistical genetic analyses and should not be understood to mean that carrying any variant in one of these genes gives an individual a 57- or 200-fold certainty of developing OCD or a tic disorder. Absolute risk can depend on the specific variant, background population and other genetic and environmental factors.

Links with other neurodevelopmental disorders

Several implicated genes have also been associated with other neurodevelopmental and psychiatric conditions, including autism spectrum disorder, developmental delay and schizophrenia.

This overlap supports evidence that diagnostic categories can share portions of their genetic architecture. It does not mean that OCD, Tourette syndrome, autism or schizophrenia are genetically equivalent conditions, nor that the same variant necessarily produces the same outcome in different individuals.

The researchers also compared their findings with genes associated with congenital heart disease, used as a non-neurological comparison condition. Significant overlap was not detected.

That comparison supports some neurological specificity in the observed enrichment, although it cannot establish that the identified genes function exclusively in the brain or are uniquely associated with OCD and tic disorders.

Long-term samples open new possibilities

The study drew on DNA collected from families over more than two decades, including more than 2,400 parent-child trios and over 1,500 individual cases.

When many of these samples were originally collected, large-scale sequencing was considerably more difficult and expensive. Advances in genomic technologies have made it possible to return to these samples and investigate rare protein-altering variants at a scale that was previously impractical.

The results demonstrate the scientific value of long-term sample collections and participation by patients and families. Combining increasingly large datasets will be particularly important because many of the variants under investigation are individually rare.

What the findings could mean for treatment

Expanding the number of strongly implicated genes gives researchers additional starting points for investigating the biology of OCD and tic disorders. The findings could help identify molecular pathways, developmental processes and neural circuits that deserve further study.

Clinical applications, however, remain uncertain. The study does not demonstrate that drugs targeting these genes or circuits would prevent or treat OCD or Tourette syndrome, and translating genetic discoveries into effective therapies can require extensive experimental and clinical research.

The findings also do not currently provide a genetic test capable of predicting whether an individual will develop either condition. OCD and tic disorders are genetically complex, and rare high-impact variants represent only part of their overall biological architecture.

Rather than providing an immediate route to personalized treatment, the research substantially expands the biological framework available for studying these disorders. Future work can investigate how the newly implicated genes affect specific cell types and developmental pathways and whether any of those mechanisms eventually yield clinically useful targets.