Genetics of obsessive-compulsive disorder: a research update

The genetic study of obsessive-compulsive disorder (OCD) has made significant gains in the past decade. However, etiological gene findings are still elusive. Epidemiological studies, including family and twin studies, strongly support a genetic component for OCD. In addition, complex segregation analyses suggest the presence of at least one major gene. The neurobiology of OCD also lends support to the notion that programmed CNS-based biological processes underlie OCD symptom expression, with mapping of brain circuits to fronto-subcortical circuits in a consistent manner. Genetic linkage studies of OCD, using families with multiple affected relatives, have generated several suggestive linkage peaks, regions that may harbor a gene or genes for OCD. However, the presence of multiple linkage peaks has added to the complexity of OCD genetics, suggesting that the exploration of gene-gene interactions and gene-environment interactions, in addition to the exploration of alternate phenotypes based on symptom expression, age at onset or comorbid conditions, may be key in locating etiologic genes. Finally, candidate gene studies, while promising, are not yet associated with linkage regions, except in the case of the glutamate transporter gene SLC1A1 in 9p24. While OCD appears to have a genetic component, additional innovative research is needed to unravel the genetic influences in the disorder.