"OCD once was thought to be primarily psychological in origin," says Yin Yao Shugart, Ph.D., 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," she says.
OCD is characterized by intrusive and senseless thoughts and impulses that together are defined as obsessions, as well as 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 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," says Jack Samuels, Ph.D., an epidemiologist and assistant professor of psychiatry at the Johns Hopkins School of Medicine.
To conduct the study, the researchers collected blood samples from 1,008 individuals from a total of 219 families in which at least two siblings were clinically diagnosed with OCD.
DNA from each sample was analyzed by the Hopkins Center for Inherited Disease Research (CIDR) 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," says Shugart, "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 says.
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," says Shugart.
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 are: Y.Y. Shugart, J. 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, all of Hopkins; B.D. Greenberg, A. Pinto and S.A. Rasmussen of Brown Medical School; J.A. Knowles, A.J. Fyer and J. Page of the College of Physicians and Surgeons at Columbia University and the New York State Psychiatric Institute; M.T. McCracken and J. Piacentini of the School of Medicine at University of California Los Angeles; S.L. Rauch and D.L. Pauls of Massachusetts General Hospital and Harvard Medical School; and D.L. Murphy of the National Institutes of Mental Health at the National Institutes of Health.
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