Yonsei Medical Journal Vol. 47, No. 4, pp. 443 - 454, 2006 Review Article The Genetic Studies of Obsessive-Compulsive Disorder and Its Future Directions Se Joo Kim and Chan-Hyung Kim Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Seoul, Korea. Obsessive-compulsive disorder (OCD) is characterized by recurrent and persistent thoughts (obsessions), and repetitive behaviors or mental acts (compulsions). In Korea, an epide- miological study reported that the lifetime prevalence of OCD in the population was greater than two percent. The exact cause of OCD is still unknown. Evidence from familial, twin and segregation studies supports the role of a genetic com- ponent in the etiology of OCD. In addition, there is growing evidence that OCD has a specific neurochemical and neuro- anatomical basis. According to this evidence, researchers have selected various candidate genes which have been implicated in the neurophysiology of OCD, and differences of allelic variants in OCD patients and controls have been analyzed. In this review we will introduce the results of previous genetic studies of OCD which have been performed in other popu- lations, including twin studies, family studies, segregation analyses, linkage analyses, and association studies. In addition to these studies, we will present the results of our genetic studies of OCD performed in Korea. Key Words: Obsessive-compulsive disorder, genetic com- ponent Obsessive-compulsive disorder (OCD) is charac- terized by recurrent and persistent thoughts (obsessions), and repetitive behaviors or mental acts (compulsions). Most patients with OCD have a chronic course of the illness and show a wide range of functional impairment in occupational and social areas. One epidemiological study reported that about 3% of the general population Received August 8, 2006 Reprint address: requests to Dr. Chan-Hyung Kim, Youngdong Severance Hospital, Department of Psychiatry, Institute of Behavioral Science in Medicine, Yonsei University College of Medicine, Dogok-dong, Gangnam-gu, Seoul 135-720, Korea. Tel: 82-2-2019-3340, Fax: 82-2-3462-4304, E-mail: spr88@yumc.yonsei. ac.kr in the U.S. has experienced OCD.1 This preva- lence is 20 times higher than previously expected. This result suggests that OCD is more common than schizophrenia or panic disorder, which are both well-known by the general population. In Korea, an epidemiological study2 reported that the lifetime prevalence of OCD in urban and rural populations were 2.29% and 2.14%, respectively. The causes of OCD are still unclear, but there is growing evidence that OCD has some specific neurobiological bases, and that one of these is a genetic component. The familial tendency of OCD has been observed since the 1930s using genetic studies of OCD. These included twin, family, segregation, and association studies, and revealed that some specific genes have an effect on the development of OCD.3 Therefore, we reviewed in this paper studies concerning the genetics of OCD using various ethnic groups, including Koreans. TWIN STUDIES Many researchers have used twin studies to estimate the relative importance of genetic and environmental factors in the development of OCD. If the concordance rate of a certain disorder between monozygotic (MZ) twins is 100%, we can conclude that the disorder is most likely purely genetic. If the MZ concordance rate is less than 100%, it means that the disorder is likely caused by a mixture of genetic and environmental factors. Also, if the concordance rate between MZ twins is much higher than that of dizygotic twins (DZ), it can be considered that a genetic component contributes substantially to the pathophysiology of the disorder.3 Inouye et al.4 reported an 80% Yonsei Med J Vol. 47, No. 4, 2006