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

项目总结 在这项研究中，我们试图了解遗传因素如何影响强迫症的发病风险。 拉丁美洲人的精神障碍(OCD)。强迫症及相关疾病对公共卫生具有重大意义。 由于他们巨大的个人和社会代价。人们对它们的病因知之甚少，而且 治疗、检测和预防策略不是最佳的，也不是以病理生理学知识为指导的。在……里面 其他精神疾病(如精神分裂症、双相情感障碍和自闭症)，基因组学已经开始提供 了解遗传结构的基础知识，识别特定的基因座以进行生物追踪和定位 在疾病中改变了路径。我们打算通过显著增加和 使用于基因组分析的全球样本量多样化，这是阐明 这种情况下的生物学。 本项目将对三个重叠区域进行调查。首先，我们将收集世界上最大的祖先- 强迫症病例样本多样(N=5,000人来自拉丁美洲)。为了以高效和成本的方式做到这一点- 有效的方式，我们将利用我们在拉丁语建立的强迫症诊所网络 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。第二，我们 将对Illumina全球筛选阵列上的所有5,000个样本进行基因分型(&gt；10,000个匹配的基因类型 控件将可用)。这将使我们能够与精神病学基因组学联盟合作， 发现存在与强迫症相关的常见变异的基因组基因座。第三，我们将精细绘制全基因组图 并计算个体多基因风险分数(PR)，以此作为强迫症遗传易感性的衡量标准。 我们预计，新纳入的祖先多样性样本将提高我们的精细测绘能力，产生更多 在非欧洲样本中进行准确的PR，并最终减少强迫症基因组时的健康差异 研究结果被用于临床。总体而言，这项研究将提高我们对因果机制的理解 与强迫症有牵连，以期改善临床结果，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.