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- 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.
- 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
- Subjects
OBSESSIVE-compulsive disorder; GENOMES; COMPULSIVE behavior; CHROMOSOMES; NEUROSES
- Publication
Molecular Psychiatry, 2006, Vol 11, Issue 8, p763
- ISSN
1359-4184
- Publication type
Article
- DOI
10.1038/sj.mp.4001847