Shared Genetics of Obsessive Compulsive Disorder in Dogs and Humans

Obsessive-compulsive disorder (OCD) is a heritable, severe mental illness manifested as time-consuming repetition of behaviors. In humans, OCD has a highly polygenic architecture that makes it difficult to identify genetic risk factors with currently attainable sample sizes. Canine OCD is a naturally occurring model for human OCD that is genetically more complex than induced animal models. Through single breed genome-wide association and subsequent targeted sequencing in multiple dog breeds, we identify genes and candidate causal variants associated with canine OCD. We then employ a canine and murine model-driven approach to reduce the genetic search space for a human association study, and identify significantly associated genes despite a modest cohort size. Our results implicate cell adhesion molecules involved in synaptic connectivity and maintenance in both dog and human OCD. Applying this approach to a wider range of complex behavioral disorders shared between dogs and humans could lead to new biological understanding and potential therapeutic targets.