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Genetic Studies Give Clues to Tourette Syndrome, OCD

By Barbara Bronson Gray
HealthDay Reporter

TUESDAY, Aug. 14 (HealthDay News) -- Two new large-scale studies searching for the genetic links to a couple of relatively common psychiatric conditions show how difficult it can be to decipher the human genome's role in disease.

The research, the first genome-wide studies looking at the potential association of particular genes with obsessive-compulsive disorder (OCD) and Tourette syndrome, was published in two reports in the Aug. 14 issue of Molecular Psychiatry.

While the studies failed to identify particular genes responsible for either of these conditions, it contributed important new clues.

"The studies suggest there are probably lots of different genes of small effect that play a role, or, perhaps, there is a rare single gene," said Dr. Francis McMahon, chief of the human genetics branch within the intramural research program at the U.S. National Institute of Mental Health.

While the research did not identify a particular gene or combination of genes responsible for either Tourette syndrome or OCD, it does contribute to the understanding of the genetic architecture of both conditions, McMahon said. "Unfortunately for those who suffer from these conditions, that means there's not much hope for a quick drug target to be developed from this research," he said.

Obsessive-compulsive disorder is an anxiety condition characterized by repetitive, recurrent thoughts and compulsions that disrupt people's lives. Tourette syndrome is a chronic, inherited disorder of the nervous system, characterized by unwanted movements and noises called "tics." It often begins in childhood and can be associated with OCD or attention-deficit/hyperactivity disorder (ADHD).

The conditions often run in families, which makes them prime targets for genetic research. Previous studies that compared affected and unaffected people were not large enough to detect specific genes or areas of the genome responsible for increasing a person's risk for either or both conditions.

Genome-wide studies, known as GWAS, look at common genetic variants among different people to find associations with diseases or traits. They compare the DNA of those with a condition to others without it.

The genetic details are analyzed, looking for gene variants that show up more frequently in people with the disease than in those without it. Variations in the individual make-up of a genome are identified by noting areas where there are changes and variations that could heighten the risk of disease.

For these studies, the International OCD Foundation Genetic Collaborative, which includes more than 20 research groups in nine countries, analyzed about 480,000 gene variants called SNPs (single-nucleotide polymorphisms) in 1,465 people with OCD, more than 5,500 without OCD, and in others including both parents of someone with the condition.

The Tourette Syndrome Association International Consortium for Genetics and the Tourette Syndrome GWAS Consortium, which includes 22 groups in seven nations, analyzed 484,000 SNPs in about 1,500 individuals against 5,250 people without Tourette syndrome.

McMahon explained that the purpose of the GWAS approach is to look across the whole genome for common forms of variation, looking for genetic differences present in a quarter, a third, or half the population. "That's where the statistical power lies," he noted.

The researchers identified a signal within a gene in people with Tourette syndrome. That gene encodes a protein in the cerebellum, an area of the brain involved in motor control. They also found that a strong signal close to another gene, active in the brain during childhood and adolescence, was associated with those with OCD, which often emerges during that particular time of life. But none of the discoveries were closely enough associated to identify risk factors.

Dr. James Leckman, a co-author of the studies and a distinguished professor of child and adolescent psychiatry at Yale University, explained that genetic analysis is complicated by the fact that while some people have just Tourette syndrome or only OCD, a percentage has both, and others also have ADHD. Some have very resistant symptoms and others are treated effectively, usually with cognitive behavioral therapy.

"GWAS studies lump everybody together but we need to tease out the differences," Leckman said. "I'm not sure the GWAS strategy will get us where we need to go."

Three of every 1,000 children have Tourette syndrome, according to the U.S. Centers for Disease Control and Prevention. The American Psychiatric Association says more than 4 million people have OCD.

"These are chronic conditions; people with OCD and Tourette's deal with it every day. Both, at their worst, are debilitating, and the anxiety is always present," said Alies Muskin, executive director of the Anxiety and Depression Association of America, in Silver Spring, Md.

Tourette syndrome and OCD can be treated with cognitive behavioral and exposure therapy, which train people to deal with their anxiety, Muskin said.

More information

The U.S. National Institute of Mental Health has more about OCD and Tourette syndrome.

SOURCES: Francis J. McMahon, M.D., chief, human genetics branch, intramural research program, U.S. National Institutes of Mental Health, Bethesda, Md.; James Leckman, M.D., Neison Harris Professor of Child and Adolescent Psychiatry, Yale University, New Haven, Conn.; Alies Muskin, executive director, Anxiety and Depression Association of America, Silver Spring, Md.; Aug. 14, 2012, Molecular Psychiatry

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