Rare Genetic Variants Increase Risk for Tourette Syndrome

An international team of 57 scientists from 11 countries has identified the first definitive risk genes for Tourette syndrome (TS), a complex neuropsychiatric disorder.

The breakthrough came when researchers focused on a relatively new area of genomics research that involves looking at the entire genome, rather than searching for a particular gene, said Dr. Peristera Paschou, Purdue University associate biology professor.

“Most times we focus on a mutation of a single base pair, which are the building blocks of DNA, and look for a mutation. But in recent years we’ve realized that there is another type of variation of the human genome,” said Paschou.

Tourette syndrome, which affects about one in 100 people, is characterized by one or more physical tics, such as throat clearing, coughing, eye blinking, or facial movements, along with at least one involuntary phonic or verbal tic.

People with TS also are more likely to have additional neuropsychiatric disorders, such as attention deficit hyperactivity disorder (ADHD) or obsessive compulsive disorder (OCD), and appear to be at greater risk for anxiety, major depression or autism spectrum disorders.

Because of the large variety of symptoms and related conditions, Tourette Syndrome is often a difficult condition to identify and track.

In recent years, however, scientists have been investigating how often short sections of genes are repeated through the entire genome, how these repetitions (called copy number variants) might vary among individuals, and whether they have an effect on health.

“These variations may involve a large part of the DNA sequence and may even include whole genes. We have only very recently begun to understand how copy number variation may relate to disease,” said Paschou.

“In the case of this research on Tourette Syndrome, we scanned the entire genome, and through physical analysis, we were able to identify where this variation lies. We rarely find variants that are associated at such a high level. This is why this is such a big breakthrough.”

Dr. Jeremiah Scharf, of the Psychiatric & Neurodevelopmental Genetics Unit in the Massachusetts General Hospital Departments of Psychiatry and Neurology and the Massachusetts General Hospital Center for Genomic Medicine, co-senior author of the report, says this is a significant finding.

“The challenge of recognizing that Tourette Syndrome is not a single gene disorder, and that a stringent statistical certainty is required in order to declare a gene to be significantly associated with it, has been our long-term aim,” he said.

“We believe that what sets our study apart from prior studies is that the two genes we have identified both surpassed the stringent threshold of ‘genome-wide significance,’ and so, represent the first two definitive Tourette Syndrome susceptibility genes.”

The research will help speed new and more effective treatments for Tourette’s as well as other disorders.

“Tourette Syndrome has long been considered a model disorder to study the parts of the brain that function at the intersection of our traditional concepts of neurology and psychiatry,” Scharf says.

“These first two definitive genes for Tourette Syndrome give us strong footholds in our efforts to understand the biology of this disease, and future studies of how these genes work both in health and disease may lead to discoveries that are more broadly relevant to neuropsychiatric disorders in general.”

Although this research was the largest ever conducted on Tourette Syndrome, Paschou says a much larger study is already being planned.

“We are hopeful that in the next two years we will put together a sample of 12,000 patients, which is something that those of us who work in this field could not have imagined before,” she said.

Paschou says that the success of the collaboration is due not just to the researchers, but also to the patients and their families. “It was such a great contribution for the patients and their families to participate in this study. Without them studies like this could not exist.”

The new findings are published in the journal Neuron.

Source: Purdue University