Rutgers-Led Team Identifies 36 Genes Tied to OCD and Tic Disorders, Opening New Treatment Targets

A Rutgers-led international collaboration has identified 36 genes that substantially raise the risk for obsessive-compulsive disorder (搜索)搜索该疾病 (OCD) and chronic tic disorders (搜索)搜索该疾病, providing what two researchers described as the most detailed biological understanding of how these conditions develop and how they might eventually be treated. The study, published in Nature Neuroscience, analyzed DNA from nearly 4,000 people diagnosed with OCD, chronic tic disorders such as Tourette syndrome (搜索)搜索该疾病, or both conditions.

Gary Heiman, a professor in the Department of Genetics in the Rutgers School of Arts and Sciences and a senior coauthor of the study, said the research "dramatically expands the catalog of shared risk genes, reveals biological connections with autism (搜索)搜索该疾病 and schizophrenia (搜索)搜索该疾病 and highlights the brain circuits that govern impulse control, movement, and habit formation."

Expanding the Genetic Landscape

Before this study, scientists had found only a few genetic clues, each linked separately to OCD or chronic tic disorders (搜索)搜索该疾病. The new work dramatically widens that picture. "In the past we knew about a couple of strong genes, so there were few opportunities for the pharmaceutical industry to develop drugs," said Jay Tischfield, a pioneer in the study of Tourette syndrome (搜索)搜索该疾病 and an emeritus Distinguished Professor in the Department of Genetics at Rutgers, and a senior coauthor of the study. "Now you've got over 30 targets, and that opens up new possibilities for treatment development."

OCD is characterized by persistent intrusive thoughts and repetitive behaviors, while chronic tic disorders (搜索)搜索该疾病, including Tourette syndrome (搜索)搜索该疾病, involve sudden, repeated movements or vocalizations that are difficult to control. Together, the conditions affect millions worldwide, often beginning in childhood, and frequently co-occur within the same individuals and families, according to the National Institutes of Health.

Shared Biology and Network Effects

Many of the newly identified genes are shared between OCD and chronic tic disorders (搜索)搜索该疾病, helping explain why the conditions often occur together in the same people and families. At the biological level, the disorders appear to involve many of the same brain pathways.

"These genes don't act individually," said Tischfield, who, along with Heiman, is also affiliated with Rutgers' Human Genetics Institute of New Jersey. "They act in networks. And now you can target whole networks, which will make it easier to design new therapies."

The researchers also found that several of the newly identified genes were previously linked to autism (搜索)搜索该疾病 and schizophrenia (搜索)搜索该疾病, reinforcing increasing evidence that multiple psychiatric conditions may stem from related disruptions in brain development and communication. Brain cells communicate using chemical signals called neurotransmitters that carry messages from one nerve cell to another, and the genes identified in the study appear to influence how those signals move through the brain's circuitry.

Toward Mechanism-Based Treatments

By revealing the biological systems behind the disorders, the findings could help scientists design drugs that target the underlying mechanisms rather than simply managing symptoms. Analyses of gene activity suggest many of the risk genes are active in regions involved in movement, decision-making and habit formation, including parts of the cortex and striatum.

"This study really moves the field forward," said Heiman. "We now have a much clearer picture of what's causing these disorders and many more directions to pursue as we work toward better treatments."

Study Design and Collaboration

The work was driven by a major international collaboration that combined genetic data from more than 30 research teams across the United States, Canada, Europe, South Korea and South America. To look for clues in the DNA, scientists used whole-exome sequencing, a technique that reads the sections of genes that instruct the body how to make proteins. Researchers compared gene sequences from affected individuals with those of their parents and controls, and in many cases identified new mutations that appeared in the child but not in either parent, helping pinpoint genes that likely play a role in the disorders.

The project was supported by grants from the National Institutes of Health, the New Venture Fund/Foundation for OCD Research, and the New Jersey Center for Tourette Syndrome (搜索)搜索该疾病. Rutgers researchers helped design the project, curated clinical data and oversaw genetic sequencing.

The researchers emphasized that the study would not have been possible without the long-term commitment of families who volunteered their DNA samples, many of whom were recruited through the New Jersey Center for Tourette Syndrome (搜索)搜索该疾病 and Associated Disorders and other research programs worldwide. "When we began collecting these samples 20 years ago, we did not yet have the rapid and cost-effective technologies we have today," said Heiman, noting that the samples were stored at the Rutgers Repository. "Families volunteered because they wanted to help scientists understand these conditions. Now, with modern genome sequencing, those samples have become incredibly valuable."

Heiman and Tischfield have collaborated on genetic studies of brain disorders since 2007. Participating organizations included the University of California, San Francisco; the University of California, Los Angeles; the University of Rochester; the University of Florida; the University of Miami Miller School of Medicine; Harvard Medical School and McLean Hospital; the University of Southern California; Johns Hopkins University; Thomas Jefferson University; Baylor College of Medicine; the University of Washington School of Medicine; Yale University; McGill University's Montreal Neurological Institute-Hospital; and various institutions within Europe, South America, and South Korea.