Gene discovery may hold key to better therapies for OCD

Researchers at Columbia University Vagelos College of Physicians and Surgeons and other institutions linked OCD to distinct genetic mutations in the first ever analysis of this kind. This research, published online in Nature Neuroscience on June 28, confirms that it is possible to target specific genes to create new OCD treatments. It also points out novel avenues of study for this often debilitating condition. OCD affects between 1% and 2% of the world's population. Genetics are well-known to play a significant role in who gets the disease. The identities of many OCD genes are not known. David Goldstein, PhD is the director of the Institute for Genomic Medicine at Columbia, and the senior author of the paper. "Many neurological disorders are influenced by strong acting mutations that can cause disease themselves," he said. These mutations are very rare, but they are important because they can be used as a starting point to develop therapeutics that target the exact underlying causes of disease. OCD has strong-acting mutations, but statistically reliable evidence is difficult to find. The "candidate gene" approach to genetics of OCD has been used in most of the previous research. This allows researchers to focus on genes that could be involved in pathogenesis and then look for genetic signatures of potential risk. Although this approach has been successful, it can be difficult to interpret statistically and miss undiscovered genes. Both funding agencies as well as the pharmaceutical industry are increasingly focusing on genome-wide analyses that can securely implicate genes in disease risk. Advertisement "The solution is to examine all genes in the genome simultaneously and see if any have significant evidence of risk-influencing ability. Goldstein says that OCD had not yet done this at scale. Goldstein's team collaborated with Gerald Nestadt MBBCh, a Johns Hopkins University psychiatrist with access to a group of OCD patients. They used this genome-wide approach that uses high-throughput sequencing in combination with computational biology techniques to identify the relevant genes from any part of the genome. Researchers compared large control groups to compare genes that encode protein in OCD patients with whole exome sequencing. Researchers from Harvard Medical School in Brooklyn, Harvard Medical School in Los Angeles, the David Geffen School of Medicine at Los Angeles, and the University of North Carolina Chapel Hill were part of the multi-institution collaboration. Analysis revealed a strong correlation between OCD, rare mutations, and OCD, especially in SLITRK5, a gene previously linked to OCD in candidate genome studies. Goldstein believes that new data on SLITRK5 could encourage translational researchers and pharmaceutical companies to develop drugs targeting this gene. This study also revealed a pattern of variation in genes. Goldstein states that genes that are resistant to variation in the human population are those most likely to cause diseases. "We see an overall increase in harmful mutations in OCD genes when compared to controls." This is a sign that OCD genes are more prevalent than we think and it's important to know where they can be found. OCD patients and their doctors need new treatment options. OCD is a disorder that causes recurring thoughts and behavior patterns that are difficult to control. H. Blair Simpson MD, PhD, is a professor of psychiatry at Columbia University Vagelos College of Physicians and Surgeons and the director of the Center for OCD & Related Disorders, New York State Psychiatric Institute. He was not involved in the new study. Simpson states that there are two options available for treating OCD. They are serotonin-reuptake inhibitor drugs and cognitive behavioral therapy. However, they only work on half of patients. These genetic findings are exciting. They suggest that precision medicine could include OCD. This will ultimately transform how we diagnose and treat OCD.


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