Thus, although they may truly be associated with the onset, severity, or persistence of OCD symptoms, they
are unlikely to cause OCD without the presence of other risk genes. On the other hand, since most current effective pharmacologic agents target the serotonergic and dopaminergic systems, it is possible that some of the genes in those systems could play a role in treatment response. Knowing which genes impact treatment response would be a major advance in the treatment of OCD and is consistent with the primary goal of the emerging field Inhibitors,research,lifescience,medical of pharmacogenetics. However, it would not necessarily demonstrate that those genes are involved in the etiology of OCD. Genes involved in response to treatment may not be involved in the etiology of a disorder. Genetic linkage studies Only three genome -wide linkage studies of OCD have been completed to date.135-137 No study yielded genomewide significance; however all studies suggested regions of interest for future research. Hanna et al136 completed Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical a genome scan on seven families which included 66 individuals. All families had been identified through childhood OCD probands. All but one of the relatives were directly assessed with structured psychiatric interviews and
32 received diagnosis of lifetime OCD. Table III Candidate gene studies of OCD. *Association with the hoarding selleckchem Paclitaxel phenotype Three
hundred forty-nine microsatellite markers were genotyped on these families. Twenty-four additional markers included in the fine-mapping subsequent to the initial genome scan. In the initial analyses a Inhibitors,research,lifescience,medical LOD score of 2.25 for marker D9S288 on chromosome 9p was observed. However, after finemapping Inhibitors,research,lifescience,medical the LOD score dropped to 1.97. In general, LOD scores above 3.6 are considered to be genome-wide significant. In an attempt to replicate these findings, Willour et al138 genotyped microsatellite markers on all available relatives in 50 pedigrees which had been ascertained through persons with OCD. The largest LOD scores observed in this study were for markers D9S1792 (HLOD=2.26) D9S1813 (NPL=2.52, P=0.006). Dacomitinib D9S1813 and D9S1792 are within 350 kb of marker D9S288, the marker yielding the largest LOD score reported by Hanna et al. The second genome-wide linkage study included a total of 219 families. Both affected sib-pair and multigenerational families were genotyped.136 Suggestive evidence was observed for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q. The strongest linkage evidence was obtained for markers on chromosome 3q27-28 when both definite and probable cases of OCD were considered affected. The maximum overall Kong and Cox LODall score (2.67) occurred with markers D3S1262 (P=0.0003) and D3S2398 (P=0.0004).