Se Joo Kim and Chan-Hyung Kim lished. Hanna and his colleagues25 analyzed a genome scan in 56 individuals from seven families ascertained through pediatric OCD probands; 27 of the 56 subjects had a lifetime diagnosis of definite OCD. Their genome scan consisted of 349 microsatellite markers with an average between- marker distance of 11.3 cM. They found that the maximum multipoint LOD score with a dominant model was 2.24 on 9p24. This result was also replicated by Willour et al.26 when they genotyped 50 pedigrees with OCD using microsatellite markers spanning the 9p24 candidate region. They also reported that a 9p24 signal was observed in both parametric and nonparametric linkage an- alyses. Recently, Shugart et al.27 conducted a genome-scan analysis of 219 families collected as part of the OCD Collaborative Genetics Study. Using the broad OCD definition, they observed the strongest evidence for linkage was on chromo- some 3q27-28. Covariate-linkage analyses impli- cated a possible role of gene on chromosome 1 in increasing the risk for an earlier-onset form of OCD. ASSOCIATION STUDIES Whereas linkage analysis focuses merely on the position of a tested marker, an association study tests whether a particular allele of a marker, a specific genotype, or a haplotype is statistically associated with affected individuals when com- pared to unaffected controls. Two design strate- gies are employed in association studies: popula- tion case-control designs and family-based asso- ciation designs. Currently, the major approach used in identifying OCD susceptibility genes has been to compare the distribution of genotypes or alleles of genes implicated in the neurophysio- logy of OCD using population- or family-based association studies.28 Genes related to serotonin neurotransmission Studies performed over the last decade have implicated the involvement of the serotonin (5- HT) system in the pathophysiology of OCD. The number of [3H] paroxetine binding sites in blood platelets has been found to be significantly lower Yonsei Med J Vol. 47, No. 4, 2006 in OCD patients than in normal controls.29 It has also been reported that m-chlorophenylpiperazine (m-CPP), a serotonergic agent, exacerbates OC symptoms.30,31 In addition, the efficacy of selective serotonin reuptake inhibitors (SSRIs) in the treat- ment of OCD has lead to the hypothesis of a serotonergic dysfunction in OCD. Therefore, most widely-investigated candidate genes of OCD are genes related to serotonergic neurotransmission. Serotonin transporter gene Since the serotonin transporter (5-HTT) is the primary target of action of SSRIs, the 5-HTT gene located on chromosome 17q12 may be a good candidate for OCD treatment. The serotonin trans- porter gene has a functional biallelic polymor- phism in the promoter region,32 consisting of an insertion (long allele, L) or a deletion (short allele, S) of 44 bp, which has been shown to have a significant effect on blood serotonin concentra- tion.33 McDougle et al.34 used a family-controlled transmission disequilibrium test (TDT) with a set of 34 European-American family trios of OCD and found that the association and linkage disequilib- rium between the 5-HTT linked the promoter region (5-HTTLPR) gene L allele with OCD. They also reported that a poor response to SSRIs might be related with the L allele. Bengel et al.35 re- cruited 75 Caucasian OCD patients and 397 ethni- cally-matched individuals from a non-patient con- trol group and found that the patients with OCD were more likely than controls to carry two copies of the L allele (46.7% vs. 32.3%). However, Kinner et al.36 did not find any significant association between the distribution of the 5-HTTLPR geno- types and OCD in 54 OCD patients of Afrikaner descent and 82 ethnically-matched control indi- viduals. Camarena et al.37 analyzed the 5-HTTLPR polymorphic system in 115 Mexican OCD patients and 136 controls. They could not find a significant association between the L allele and OCD in both case-control and family-based designs, including haplotype-based haplotype relative risk (HHRR) and TDT. Many other studies performed in various populations including Jewish,38 German,39 French,40 etc.41 also did not find a significant association between 5-HTTLPR polymorphism and OCD. In Korea, there has been only one study of the association between 5-HTTLPR and OCD. We