Bibliographic Details
| Title: |
Genomewide linkage scan for obsessive-compulsive disorder: evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q. |
| Authors: |
Shugart, Y. Y., Samuels, J., Willour, V. L., Grados, M. A., Greenberg, B. D., Knowles, J. A., McCracken, J. T., Rauch, S. L., Murphy, D. L., Wang, Y., Pinto, A., Fyer, A. J., Piacentini, J., Pauls, D. L., Cullen, B., Page, J., Rasmussen, S. A., Bienvenu, O. J., Hoehn-Saric, R., Valle, D. |
| Source: |
Molecular Psychiatry. Aug2006, Vol. 11 Issue 8, p763-770. 8p. 1 Diagram, 3 Charts, 5 Graphs. |
| Subjects: |
Obsessive-compulsive disorder, Genomes, Compulsive behavior, Chromosomes, Neuroses |
| Abstract: |
Obsessive-compulsive disorder (OCD) is the tenth most disabling medical condition worldwide. Twin and family studies implicate a genetic etiology for this disorder, although specific genes have yet to be identified. Here, we present the first large-scale model-free linkage analysis of both extended and nuclear families using both ‘broad’ (definite and probable diagnoses) and ‘narrow’ (definite only) definitions of OCD. We conducted a genome-scan analysis of 219 families collected as part of the OCD Collaborative Genetics Study. Suggestive linkage signals were revealed by multipoint analysis on chromosomes 3q27–28 (P=0.0003), 6q (P=0.003), 7p (P=0.001), 1q (P=0.003), and 15q (P=0.006). Using the ‘broad’ OCD definition, we observed the strongest evidence for linkage on chromosome 3q27-28. The maximum overall Kong and Cox LODall score (2.67) occurred at D3S1262 and D3S2398, and simulation based P-values for these two signals were 0.0003 and 0.0004, respectively, although for both signals, the simulation-based genome-wide significance levels were 0.055. Covariate-linkage analyses implicated a possible role of gene(s) on chromosome 1 in increasing the risk for an earlier onset form of OCD. We are currently pursuing fine mapping in the five regions giving suggestive signals, with a particular focus on 3q27–28. Given probable etiologic heterogeneity in OCD, mapping gene(s) involved in the disorder may be enhanced by replication studies, large-scale family-based linkage studies, and the application of novel statistical methods.Molecular Psychiatry (2006) 11, 763–770. doi:10.1038/sj.mp.4001847; published online 6 June 2006 [ABSTRACT FROM AUTHOR] |
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| Database: |
Psychology and Behavioral Sciences Collection |