Journal article
Genomewide linkage scan for obsessive-compulsive disorder : evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q
Molecular psychiatry, Vol.11(8), pp.763-770
2006
DOI: 10.1038/sj.mp.4001847
PMID: 16755275
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.
Details
- Title: Subtitle
- Genomewide linkage scan for obsessive-compulsive disorder : evidence for susceptibility loci on chromosomes 3q, 7p, 1q, 15q, and 6q
- Creators
- Y. Y SHUGART - Department of Epidemiology, Johns Hopkins University, Baltimore, MD, United StatesJ SAMUELS - Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesA PINTO - Department of Psychiatry and Human Behavior, Brown Medical School, Butler Hospital, Providence, RI, United StatesA. J FYER - Department of Psychiatry, College of Physicians and Surgeons at Columbia University and the New York State Psychiatric Institute, New York, NY, United StatesJ PIACENTINI - Department of Psychiatry and Biobehavioral Sciences, School of Medicine, University of California, Los Angeles, CA, United StatesD. L PAULS - Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesB CULLEN - Department of Psychiatry, Johns Hopkins University, Baltimore, MD, United StatesJ PAGE - Department of Psychiatry, College of Physicians and Surgeons at Columbia University and the New York State Psychiatric Institute, New York, NY, United StatesS. A RASMUSSEN - Department of Psychiatry and Human Behavior, Brown Medical School, Butler Hospital, Providence, RI, United StatesO. J BIENVENU - Department of Psychiatry, Johns Hopkins University, Baltimore, MD, United StatesR HOEHN-SARIC - Department of Psychiatry, Johns Hopkins University, Baltimore, MD, United StatesD VALLE - Department of Behavioral Sciences and Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesV. L WILLOUR - Department of Psychiatry, Johns Hopkins University, Baltimore, MD, United StatesK.-Y LIANG - Department of Biostatistics, Johns Hopkins University, Baltimore, MD, United StatesM. A RIDDLE - Department of Behavioral Sciences and Pediatrics, School of Medicine, Johns Hopkins University, Baltimore, MD, United StatesG NESTADT - Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, United StatesM. A GRADOS - Department of Psychiatry, Johns Hopkins University, Baltimore, MD, United StatesB. D GREENBERG - Department of Psychiatry and Human Behavior, Brown Medical School, Butler Hospital, Providence, RI, United StatesJ. A KNOWLES - Department of Psychiatry, College of Physicians and Surgeons at Columbia University and the New York State Psychiatric Institute, New York, NY, United StatesJ. T MCCRACKEN - Department of Psychiatry and Biobehavioral Sciences, School of Medicine, University of California, Los Angeles, CA, United StatesS. L RAUCH - Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United StatesD. L MURPHY - Laboratory of Clinical Science, NIMH, NIH, Bethesda, MD, United StatesY WANG - Department of Psychiatry, Johns Hopkins University, Baltimore, MD, United States
- Resource Type
- Journal article
- Publication Details
- Molecular psychiatry, Vol.11(8), pp.763-770
- DOI
- 10.1038/sj.mp.4001847
- PMID
- 16755275
- NLM abbreviation
- Mol Psychiatry
- ISSN
- 1359-4184
- eISSN
- 1476-5578
- Publisher
- Nature Publishing Group; Basingstoke
- Language
- English
- Date published
- 2006
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984070270102771
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