Wayne State contributes to massive international effort examining genetic underpinnings of obsessive-compulsive disorder
Wayne State University is among the research universities involved in a major step forward in obsessive-compulsive disorder genomics.
School of Medicine Professor and Chair of Psychiatry and Behavioral Neurosciences David Rosenberg, M.D., is Wayne State’s site leader on “Genome-wide analyses identify 30 loci associated with obsessive–compulsive disorder,” an open access article published in Nature Genetics that details one of the largest and most well-powered analyses of its kind to date, with a 20-fold increase of OCD cases compared to previously published studies.
The chronic psychiatric disorder affects up to 3% of the American population and is characterized by obsessions and compulsions that vary in type and severity. Wayne State and Dr. Rosenberg, the Miriam L. Hamburger Endowed Chair of Child Psychiatry, was part of an international group conducting the genome-wide association study meta-analysis of 28 OCD case–control cohorts of European ancestry, combining 53,660 OCD cases and 2,044,417 controls that identified 30 independent genome-wide significant loci, a fixed position where a specific gene lives. Cases came from a variety of sources, included 30,000 from 23andMe Inc., as well as from clinical health records and biobanks.
OCD is responsible for profound personal and societal costs, including increased risk of suicide and overall mortality.
“I believe that this represents a major advance as the study identified new OCD genetic risk markers and potential candidate causal genes," Dr. Rosenberg said. "What is especially exciting is our group and others have found that the brain regions where these candidate causal genes are expressed are exactly the brain regions identified in brain imaging studies most implicated in OCD. OCD also appears to share genetic risk with Tourette syndrome, depression and anorexia nervosa.”
Gene-based approaches identified 249 potential effector genes for OCD, with 25 classified as the most likely causal candidates and multiple genes in the major histocompatibility complex region. The study estimated that 11,500 genetic variants explained 90% of OCD genetic heritability.
OCD genetic risk was associated with excitatory neurons in the hippocampus and the cortex, along with D1 and D2 type dopamine receptor-containing medium spiny neurons. OCD genetic risk was shared with 65 of 112 additional phenotypes, including all the psychiatric disorders they examined. In particular, OCD shared genetic risk with anxiety, depression, anorexia nervosa and Tourette syndrome and was negatively associated with inflammatory bowel diseases, educational attainment and body mass index.
“This is an amazing advancement with implications not just for OCD but for multiple other neuropsychiatric disorders,” Dr. Rosenberg said.” It has been a great honor to be part of an expert consortium such as this and site leader at WSU. It is only via these multi-site consortia that we are able to recruit large samples to really do a deep dive into the genetic underpinnings of a disorder such as OCD.”