Addition of OCD to the Genomic Psychiatry Cohort

该项目通过确定和招募5，000名患有强迫症（OCD）的患者，并对5，000名OCD患者和5，000名已经确定和基因分型的无OCD匹配对照进行全基因组关联研究（GWAS），为基因组精神病学队列（GPC）的扩展提供资金。这项研究是实现发现所需统计能力的关键一步。我们将使全球范围内可用于OCD的GWAS参与者总数增加一倍以上，并为OCD创建唯一的大型可重新联系队列。GPC是一个大型（n= 33，000）、基于南加州大学的临床队列，旨在成为大规模基因组研究、关注RDoC和/或其他替代表型构建体的研究、巢式病例对照/临床研究、长期病程研究和基因组变体-表型研究的主要资源（Pato et al，2013）。此外，GPC是“开源”的，因为经批准的非USC研究者可以访问该队列进行额外的合作研究。GPC目前由精神分裂症患者（n= 10，000）、双相情感障碍患者（n= 5，000）、这些患者的家庭成员（n= 3，000）和无强迫症、精神分裂症或双相情感障碍病史或家族史的对照参与者（n= 15，000）组成。我们能够重新联系超过88%的参与者。建议的GPC-OCD队列和我们已证明的满足或超过大规模遗传研究样本收集目标的记录，使我们能够通过以下方式在理解OCD的分子基础方面取得进一步进展：（i）发现其他遗传风险因素（罕见和常见）;和（ii）鉴定足够大的一组特定遗传变异以研究它们如何在所有水平上与神经精神表型相关，包括，但不限于，疾病本身。

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.