Genetics of Obsessive-Compulsive Disorder may also be functionally involved in OCD. Zai et al.92 investigated five polymorphisms in the GABA type B receptor 1 (GABBR1) gene in 159 OCD probands and their families using the TDT, and they found a trend with an over-transmission of the -7265A allele at the A-7265G polymorphism in OCD. Hall et al.93 evaluated a possible role of the BDNF gene in 164 triads with OCD and suggested that the Met66 allele, which affects the sequence of the proBDNF protein, is undertransmitted and likely confers a protective effect against OCD. FUTURE DIRECTIONS The genetic research of OCD has been much advanced during the past decade. However, like in other psychiatric disorders, the genetic study of OCD has several limitations that should be overcome. First, OCD is not a homogenous condi- tion, and there might be various underlying etio- logical mechanisms of OCD. Therefore, the ability to define genetically valid subgroups of OCD is crucial for genetic studies of OCD. Miguel et al.94 suggested several strategies for identifying valid OCD phenotypes as follows. 1) The categorical approaches: early-onset OCD phenotype, tic-re- lated OCD phenotype and sensory phenomena as a component of the OCD phenotype, and 2) the dimensional approaches: OCD symptom dimen- sions and quantitative personality traits related to OCD. Another approach to identify more homo- genous OCD subtypes is to find endophenotypes, including brain-based markers (i.e., neuroimaging and neurophysiological findings). Second, the genotypes' distribution of genes is not the same according to ethnicity. As mentioned above, genotype distributions of various genes in Asians (including Koreans) are quite different from those in the Western population. Therefore, it could not be assumed that the results from Western popu- lations would be replicated in Asian populations, including Koreans. In addition, most genetic studies of OCD did not have a sufficient sample size to draw clear conclusions. Therefore, if more large-scale studies using large sample sizes would be performed in various populations, it would be helpful to understanding the genetic contribution to OCD. REFERENCES 1. Karno M, Golding JM, Sorenson SB, Burnam MA. The epidemiology of obsessive-compulsive disorder in five US communities. Arch Gen Psychiatry 1988;45:1094-9. 2. Lee JK. A nationwide epidemiological study of mental disorders in Korea (XIII)-obsessive-compulsive dis- order. J Korean Neuropsychiatr Assoc 1994;33:5-17. 3. Wolff M, Alsobrook JP, 2nd, Pauls DL. Genetic aspects of obsessive-compulsive disorder. Psychiatr Clin North Am 2000;23:535-44. 4. Inouye E. Similar and dissimilar manifestations of ob- sessive-compulsive neuroses in monozygotic twins. Am J Psychiatry 1965;121:1171-5. 5. Carey G, Gottesman II. Twin and family studies of anxiety, phobic, and obsessive disorders. In: Klein D, Rabkin J, editors. Anxiety: new research and changing concept. New York: Raven Press; 1981. p.117-36. 6. Clomipramine Collaborative Study Group. Clomipramine in the treatment of patients with obsessive-compulsive disorder. Arch Gen Psychiatry 1991;48:730-8. 7. Chouinard G. Sertraline in the treatment of obsessive compulsive disorder: two double-blind, placebo-con- trolled studies. Int Clin Psychopharmacol 1992;7 Suppl 2:37-41. 8. van Grootheest DS, Cath DC, Beekman AT, Boomsma DI. Twin studies on obsessive-compulsive disorder: a review. Twin Res Hum Genet 2005;8:450-8. 9. Hemmings SM, Stein DJ. The current status of associa- tion studies in obsessive-compulsive disorder. Psychiatr Clin North Am 2006;29:411-44. 10. Lewis A. Problems of obsessional illness. Proc Roy Soc Med 1935;29:325-36. 11. Rasmussen SA, Tsuang MT. Clinical characteristics and famil history in DSM-III obsessive-compulsive disorder. Am J Psychiatry 1986;143:317-22. 12. Riddle MA, Scahill L, King R, Hardin MT, Towbin KE, Ort SI, et al. Obsessive compulsive disorder in children and adolescents: phenomenology and family history. J Am Acad Child Adolesc Psychiatry 1990;29:766-72. 13. Bellodi L, Sciuto G, Diaferia G, Ronchi P, Smeraldi E. Psychiatric disorders in the families of patients with obsessive-compulsive disorder. Psychiatry Res 1992;42: 111-20. 14. Pauls DL, Alsobrook JP, Goodman W, Rasmussen S, Leckman JF. A family study of obsessive-compulsive disorder. Am J Psychiatry 1995;152:76-84. 15. Nestadt G, Samuels J, Riddle M, Bienvenu OJ 3rd, Liang KY, LaBuda M, et al. A family study of obses- sive-compulsive disorder. Arch Gen Psychiatry 2000;57: 358-63. 16. Fyer AJ, Lipsitz JD, Mannuzza S, Aronowitz B, Chapman TF. A direct interview family study of obsessive-com- pulsive disorder. I. Psychol Med 2005;35:1611-21. Yonsei Med J Vol. 47, No. 4, 2006