DESCRIPTION (provided by applicant): This project funds the expansion the Genomic Psychiatry Cohort (GPC) by ascertaining and enrolling 5,000 patients suffering from Obsessive-Compulsive Disorder (OCD) and performing a genome-wide association study (GWAS) on 5,000 OCD patients and 5,000 already ascertained and genotyped OCD-free matched controls. This study is a critical step to achieving the necessary statistical power for discovery. We will more than double the total number of available world-wide participants for GWAS of OCD, and create the only large re-contactable cohort for OCD. The GPC is a large (n=33,000), USC-based, clinical cohort designed to be a major resource for large-scale genomic studies, studies focusing on RDoC and/or other alternate phenotype constructs, nested case- control/clinical studies, long-term disease course studies, and genomic variant-to-phenotype studies (Pato et al, 2013). Additionally, the GPC is "Open Source" in that the cohort can be accessed for additional collaborative studies by approved non-USC based investigators. The GPC is currently composed of patients with schizophrenia (n=10,000), patients with bipolar disorder (n=5,000), family members of these patients (n=3,000) and control participants with no history or family history of OCD, schizophrenia or bipolar disorder (n=15,000). We are able to re-contact more than 88% of the participants. The proposed GPC-OCD cohort and our proven track record of meeting, or exceeding, the sample collection goals for large-scale genetic studies positions us very well to make further progress in understanding the molecular basis of OCD by (i) the discovery of additional genetic risk factors (rare and common); and (ii) identifying a large enough group of specific genetic variations to study how they relate to neuropsychiatric phenotypes at all levels, including, but not limited to, the illnesses themselves.

PUBLIC HEALTH RELEVANCE: Obsessive-compulsive disorder (OCD) is characterized by the presence of obsessions (thoughts) and/or compulsions (behaviors) that are distressing, time consuming and/or significantly impairing. With a lifetime prevalence of 1-3%, OCD is a leading global cause of non-fatal illness burden. Both genetic and environment factors influence the development of OCD, but inadequate sample sizes have limited the findings. Ascertainment and genetic analysis of a single large cohort of uniformly defined OCD cases and controls will provide an essential resource to the field for the identification of underlying causes of OCD.