Genomewide linkage scan for obsessive-compulsive disorder: Evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q

Y. Y. Shugart, J. Samuels, V. L. Willour, M. A. Grados, B. D. Greenberg, J. A. Knowles, J. T. McCracken, S. L. Rauch, D. L. Murphy, Y. Wang, A. Pinto, A. J. Fyer, J. Piacentini, D. L. Pauls, B. Cullen, J. Page, S. A. Rasmussen, O. J. Bienvenu, R. Hoehn-Saric, D. ValleK. Y. Liang, M. A. Riddle, G. Nestadt

Research output: Contribution to journalArticle

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 LOD all 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.

Original languageEnglish (US)
Pages (from-to)763-770
Number of pages8
JournalMolecular psychiatry
Volume11
Issue number8
DOIs
StatePublished - Aug 16 2006

Keywords

  • Age of onset
  • Covariate based linkage analysis
  • Genome-wide scan
  • Obsessive-compulsive disorder
  • Simulation

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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    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., ... Nestadt, G. (2006). Genomewide linkage scan for obsessive-compulsive disorder: Evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q. Molecular psychiatry, 11(8), 763-770. https://doi.org/10.1038/sj.mp.4001847