The Genetics of Obsessive-Compulsive Disorder

OCD is a psychiatric disorder with a lifetime prevalence of 1-3% and is a significant cause of disability worldwide. Family studies indicate that OCD has a significant hereditable component, with relatives of OCD cases being 4 times more likely to develop the disorder than the general population. Linkage studies in OCD have generally been underpowered and have failed to reach the statistical threshold for genome-wide significance, but they have nevertheless been useful for revealing potential regions of interest for future candidate gene studies. Candidate gene studies in OCD have thus far focused on genes involved in the serotonergic, dopaminergic, and glutamatergic pathways. These studies have been for the most part inconclusive, and failures to replicate have been the norm until very recently. The only genetic association replicated by multiple groups was with a glutamate transporter gene (SLC1A1). Genome-wide association studies in OCD are in progress, but final results have not yet been reported. As with the study of many other psychiatric disorders, an improved understanding of OCD will only be achieved (1) with larger collaborative efforts involving more probands, (2) the use of probands and controls drawn from epidemiologically-based populations rather than clinical samples, (3) developing a more precise phenotypic description of OCD and (4) measuring important environmental influences that affect OCD pathogenesis and severity.