Genetic susceptibility in obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) is present in 1.5-2.5% of the population and can result in substantial lifelong disability. It is characterized by intrusive thoughts, sensations, and urges and by repetitive behaviors that are difficult to control despite, in most cases, preserved insight as to their excessive or irrational nature. The causes and underlying pathophysiology of OCD are not well understood, which has limited the development of new treatments and interventions. Despite evidence for a substantial genetic contribution to disease risk, identification and replication of genetic variants associated with OCD have been challenging. Decades of candidate gene association studies have provided little insight. They are now being supplanted by modern genomewide approaches to discover both common and rare sequence and structural variants. Studies to date suggest potential novel therapeutic avenues such as modulators of glutamatergic and immune pathways; however, individual genetic findings are not yet statistically robust or replicated. Further efforts are clearly needed to identify specific risk variants and to confirm vulnerable pathways by studying much larger cohorts of patients with comprehensive variant discovery approaches. Mouse knockout models have already made notable inroads into our understanding of OCD pathology; their utility will only increase as specific risk alleles are identified.