2/2 TRANS-ANCESTRY GENOMIC ANALYSIS OF OBSESSIVE COMPULSIVE DISORDER

2/2 强迫症的跨祖先基因组分析

基本信息

批准号：
10261969
负责人：
ERIC A. STORCH
金额：
$ 43.23万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-08-17 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10261969
关键词：
Address Area Argentina Bioethics Biological Biology Bipolar Disorder Brazil Chile Chronic Clinic Clinical Cohort Studies Collaborations Colombia DNA Data Detection Diagnosis Dimensions Disease Ecuador Environment Etiology European Functional disorder Funding Future Genes Genetic Genetic Diseases Genetic study Genomics Genotype Goals Human Individual Knowledge Latin America Latin American Latinx Learning Linkage Disequilibrium Maps Measures Mental Health Mental disorders Meta-Analysis Mexico Obsessive-Compulsive Disorder Online Systems Outcome Pathway interactions Patients Performance Phenotype Population Prevention strategy Public Health Risk Saliva Sample Size Sampling Schizophrenia Science Severities Societies Specialist Structure Symptoms Testing Training Variant Work associated symptom autism spectrum disorder base case control cohort comorbidity cost cost effective design disorder risk follow-up genetic analysis genetic architecture genome wide association study genome-wide genomic locus health disparity high risk improved neuropsychiatry novel phenotypic data polygenic risk score precision medicine psychiatric genomics recruit risk variant screening societal costs working group

项目摘要

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.

项目概要在这项研究中，我们试图了解遗传因素如何影响患强迫症的风险拉丁美洲人的强迫症（OCD）和相关疾病具有重大的公共卫生重要性。由于其深刻的个人和社会成本，人们对其病因知之甚少。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。其他精神疾病（例如精神分裂症、双相情感障碍和自闭症），基因组学已开始提供有关遗传结构的基础知识，确定生物学后续的特定位点并定位我们打算通过显着增加和改变疾病的途径来实现强迫症的同样进展。使基因组分析的全球样本量多样化，这是阐明基本原理的第一步这种情况的生物学。该项目将调查三个重叠区域，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（N = 5,000 名来自拉丁美洲的人）以高效且成本低廉的方式做到这一点。以有效的方式，我们将利用我们在拉丁语地区建立的强迫症诊所网络美国，除了美国的诊所和基于网络的招募之外，还将收集表型数据。包括详细的临床特征，包括合并症和强迫症症状维度其次，我们。将在 Illumina Global Screening Array 上对所有 5,000 个样本进行基因分型（>10,000 个匹配的基因分型控制将可用）。这将使我们能够与精神病学基因组学联盟合作，发现含有与强迫症相关的常见变异的基因组位点第三，我们将精细绘制全基因组图谱。显着位点并计算个体多基因风险评分（PRS）作为强迫症遗传倾向的衡量标准。我们期望新加入的祖先多样化样本能够提高我们的精细绘图能力，从而产生更多在非欧洲样本中进行准确的 PRS，并最终减少强迫症基因组时的健康差异总的来说，这项研究将提高我们对因果机制的理解。涉及强迫症，以改善临床结果并减少慢性病和社会成本。