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

2/2 强迫症的跨祖先基因组分析

• 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
• 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

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.

项目摘要 在这项研究中，我们试图了解遗传因素如何影响发展强迫症的风险 拉丁美洲个体中的疾病（OCD）。强迫症和相关疾病至关重要 由于他们的个人和社会成本。对他们的病因少得多，并且 治疗，检测和预防策略不是病理生理知识的最佳或指导。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，确定特定的生物跟进的地方并本地化 疾病改变的途径。我们打算通过明显增加和 为基因组分析的全球样本量多样化，在阐明基本的第一步 这种情况的生物学。 该项目将研究三个重叠的区域。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名拉丁美洲的人）。以高效且成本 - 有效的方式，我们将利用我们在拉丁语中建立的OCD诊所网络 除了美国和基于Web的招聘外，美国。收集的表型数据将 包括详细的临床表征，包括合并症和强迫症符号维度。第二，我们 将在Illumina Global筛​​选阵列上的所有5,000个样品（基因型匹配的基因型）上的所有5,000个样品 控件将可用）。这将使我们能够与精神病基因组学联盟合作 发现具有与强迫症相关的常见变异的基因组基因座。第三，我们将细微地图全基因组细化 重要的局部和计算单个多基因风险评分（PR），以衡量强迫症的遗传责任。 我们希望新的祖先多样化样本的新包含能够提高我们的精细图映射能力，从而产生更多 在非欧洲样本中的准确PR，最终在强迫基因组时减少健康差异 发现在临床上使用。总体而言，这项研究将提高我们对因果机制的理解 在强迫症中实施，以改善临床结果并降低慢性和社会成本。