The role of clinical phenotypes in understanding the genetics of obsessive–compulsive disorder

Studies have shown that genetic factors are significant in predisposing individuals to obsessive–compulsive disorder (OCD). Family studies have demonstrated significantly higher rates of OCD in parents and siblings of OCD probands with an age-corrected morbid risk ranging from approximately 10% to 35% in first-degree relatives. Twin studies suggest that this familiality is, in part, due to genetic factors, and results from complex segregation analyses imply the existence of genes that have major effects on the transmission of OCD. However, not all cases of OCD seem to be familial. Furthermore, it appears that even in the familial form, there are clinical and genetic heterogeneities. Thus, future studies should either adjust the prevalence rates used in genetic analyses to account for nonfamilial cases or perform separate analyses of those families with a demonstrably familial form of OCD. Furthermore, in complex psychiatric disorders such as OCD, a single genetic locus may influence only a small part of phenotypic variance, and other genetic and environmental factors may interact in determining clinical phenotype. The implications of this finding on clinical and genetic heterogeneity in OCD are discussed.