The aim of this study is to identify susceptibility genes for OCD. We propose to recruit a sample of 350 pairs of siblings each with a strict DSM-IV diagnosis of OCD augmented with 200 extended pedigree families. To accomplish this, we have organized a group of six collaborating academic centers, each with rich clinical populations and research experience studying this condition. These centers are: Johns Hopkins University, the National Institute of Mental Health, Harvard University, Brown University, Columbia University, and the University of California at Los Angeles. The phenotypic assessments will be thorough and ensure comparability of the clinical information across all centers. There will be an emphasis on descriptive clinical material because we recognize both the importance of an accurate classification of the phenotype and-the need to explore potential homogeneous subclasses within the disorder which could facilitate the discovery of relevant genes. A genome-wide scan at ten centimorgan intervals will be conducted. Based on the results of linkage analyses, the more promising chromosomal regions will be investigated further. Materials will be made accessible to the public. The discovery of the genetic etiology of OCD should foster understanding of the pathophysiology and consequently improve the treatment and the lives of our patients. This goal is both appropriate and attainable. It is appropriate in that although we have made strides in our treatments, we continue to see patients in our clinics for whom treatments are ineffective and whose lives are substantially compromised. It is attainable because we have strong evidence at our disposal that OCD is a familial condition and molecular genetic methods are sufficiently advanced to provide the methods to detect the responsible genes even in conditions which have a complex pattern of inheritance and which may exhibit genetic heterogeneity.
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