1/2 Trans-ancestry genomic analysis of obsessive-compulsive disorder

项目摘要 在这项研究中，我们试图了解遗传因素是如何影响发展强迫症的风险的。 强迫症（OCD）在拉丁美洲的个人。强迫症和相关疾病具有重大的公共卫生意义 这是因为他们付出了巨大的个人和社会代价。关于它们的病因学知之甚少， 治疗、检测和预防策略不是最佳的，也不是由病理生理学知识指导的。在 其他精神疾病（例如，精神分裂症、躁郁症和自闭症），基因组学已经开始提供 关于遗传结构的基本知识，确定生物学随访和定位的特定位点 在疾病中改变的途径。我们打算通过显著增加和 使全球基因组分析的样本量多样化，这是阐明基因组学基本原理的第一步。 这种情况的生物学。 本项目将调查三个相互重叠的领域。首先，我们将收集世界上最大的祖先- 强迫症病例的不同样本（来自拉丁美洲的N = 5，000人）。以一种高效和低成本的方式- 我们将利用我们在拉丁美洲建立的强迫症诊所网络， 美国，除了在美国的诊所和基于网络的招聘。收集的表型数据将 包括详细的临床特征，包括合并症和强迫症症状维度。二是 将在Illumina全球筛查阵列上对所有5，000个样本进行基因分型（> 10，000个匹配的基因型 控制将可用）。这将使我们能够与精神病基因组学联盟合作， 发现与强迫症相关的常见变异的基因组位点。第三，我们将在全基因组范围内精细绘制 显著位点，并计算个体多基因风险评分（PRS）作为对OCD遗传易感性的量度。 我们希望新纳入的祖先多样性样本能够提高我们的精细映射能力， 在非欧洲样本中进行准确的PRS，并最终减少OCD基因组 研究结果用于临床。总的来说，这项研究将提高我们对因果机制的理解 与强迫症有关，以期改善临床结果并降低慢性病和社会成本。

PROJECT SUMMARY In this study we seek to understand how genetic factors influence the risk of developing obsessive-compulsive disorder (OCD) in Latin American individuals. OCD and related disorders are of major public health importance owing to their profound personal and societal costs. Little is known for certain about their etiology, and treatment, detection and prevention strategies are not optimal or directed by knowledge of pathophysiology. In other psychiatric disorders (e.g., schizophrenia, bipolar disorder, and autism), genomics has begun to deliver fundamental knowledge about genetic architecture, identify specific loci for biological follow-up and localize pathways altered in disease. We intend to realize these same advances for OCD by markedly increasing and diversifying the worldwide sample size for genomic analysis, in a first step toward elucidating the fundamental biology of this condition. Three overlapping areas will be investigated in this project. First, we will collect the world’s largest ancestrally- diverse sample of OCD cases (N = 5,000 individuals from Latin America). To do this in an efficient and cost- effective manner, we will take advantage of a network of OCD clinics we have established across Latin America, in addition to clinics in the USA and web-based recruitment. The phenotypic data collected will include a detailed clinical characterization including comorbidities and OCD symptom dimensions. Second, we will genotype all 5,000 samples on the Illumina Global Screening Array (genotypes for >10,000 matched controls will be available). This will allow us to, in collaboration with the Psychiatric Genomics Consortium, discover genomic loci harboring common variation associated with OCD. Third, we will fine-map genome-wide significant loci and calculate individual polygenic risk scores (PRS) as a measure of genetic liability to OCD. We expect the new inclusion of ancestrally diverse samples to improve our fine-mapping ability, to yield more accurate PRS in non-European samples and ultimately to reduce health disparities when OCD genomic findings are used clinically. Overall, this study will improve our understanding of the causal mechanisms implicated in OCD, with a view towards improving clinical outcomes and reducing chronicity and societal costs.