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The newspaper of The Johns Hopkins University October 2, 2006 | Vol. 36 No. 5
 
Whole-Genome Scan for OCD Links Reveals Genetic Susceptibility

By Audrey Huang
Johns Hopkins Medicine

A federally funded team of researchers including several from Johns Hopkins has identified six regions of the human genome that might play a role in susceptibility to obsessive compulsive disorder.

"OCD once was thought to be primarily psychological in origin," said Yin Yao Shugart, statistical geneticist and associate professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health. "But now there is growing evidence that there is a genetic basis behind OCD, which will help us better understand the condition."

OCD is characterized by intrusive and senseless thoughts and impulses that together are defined as obsessions, along with repetitive and intentional behaviors, referred to as compulsions. OCD is estimated to affect up to 3 percent of the American population.

In what the research team describes as the first whole-genome scan to look for genetic "markers" or similarities in the genomes of people with OCD, results identified six potentially significant regions in the genome, which lie on five different chromosomes, that appear "linked" to OCD. It's likely that any genes directly associated with OCD are to be found in these regions.

"We've long suspected that rather than being caused by a single gene, OCD has multiple genetic associations," said Jack Samuels, an epidemiologist and assistant professor of psychiatry at the Johns Hopkins School of Medicine.

To conduct the study, which was published online June 6 in Molecular Psychiatry, the researchers collected blood samples from 1,008 individuals from 219 families in which at least two siblings were clinically diagnosed with OCD.

DNA from each sample was analyzed by the Johns Hopkins Center for Inherited Disease Research using both molecular biology and statistical analysis computer programs. Specific DNA sequences — known as genetic markers — on chromosomes 1, 7, 6 and 15 and two markers on chromosome 3 appear more frequently in the patients with OCD than in those without it. The researchers want to further analyze the genetic regions they identified in this report and use more markers to possibly narrow down these regions to identify OCD risk genes.

The researchers suggest that whatever genes are found don't directly cause OCD but increase risk for it in conjunction with other genes or environmental factors.

"OCD is a relative newcomer to these genetic linkage studies," Shugart said, "so it's extremely important to follow up these findings by looking at more families and using more markers to assess the role of gene-environment interactions in OCD. "We are also very interested in finding genes underlying the different subtypes of OCD," she said.

Careful genetic analysis of different clinical categories of OCD has been limited by currently existing computer programs used in analyzing this type of data. The vast amount of data used in whole-genome analysis requires fine-tuned statistical calculations. The research team is eager to develop new methods in this area. "We predict that such findings may have immediate clinical implications for OCD patients," Shugart said.

The researchers were funded by the National Institute of Mental Health, the National Institutes of Health and the Johns Hopkins Bloomberg School of Public Health.

Authors on the paper from Johns Hopkins are Shugart, Samuels, V.L. Willour, M.A. Grados, Y. Wang, B. Cullen, R. Hoehn-Saric, D. Valle, K.-Y. Liang, M.A. Riddle and G. Nestadt.

 

Related Web sites

OCD research at Johns Hopkins
Johns Hopkins Center for Inherited Disease Research

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