Psychiatric Genomics Consortium for PTSD

创伤后应激障碍 (PTSD) 精神病学基因组学联盟

• 批准号: 10119791
• 负责人: KARESTAN C KOENEN
• 金额: $ 19.06万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-19 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10119791
• 关键词: American; Anorexia Nervosa; Architecture; Attention deficit hyperactivity disorder; Biological; Biological Process; Bipolar Disorder; Chronic; Collaborations; Complement; Copy Number Polymorphism; Country; Data; Data Set; Detection; Development; Diagnosis; Disease; Drug Use Disorder; Environment; Environmental Risk Factor; Exposure to; Family; Family Study; Funding; Genes; Genetic; Genetic Risk; Genetic Variation; Genomic approach; Genomics; Genotype; Gilles de la Tourette syndrome; Hereditary Disease; Heritability; Individual; Institutes; Institution; Interpersonal Violence; Intervention; Life; Major Depressive Disorder; Measures; Mental disorders; Meta-Analysis; Minority; Molecular; National Institute of Mental Health; Neurobiology; Numbness; Pathway Analysis; Pathway interactions; Persons; Phenotype; Post-Traumatic Stress Disorders; Prevalence; Prevention; Psychiatry; Recording of previous events; Research Personnel; Risk; Risk Factors; Sample Size; Sampling; Schizophrenia; Scientist; Severities; Strategic Planning; Symptoms; Syndrome; Testing; Time; Trauma; Twin Multiple Birth; Twin Studies; United States National Institutes of Health; Variant; Work; autism spectrum disorder; case control; cohort; data harmonization; disorder risk; experience; genetic architecture; genetic risk factor; genetic variant; genome wide association study; genome-wide; genomic locus; improved; novel; pediatric trauma; phenotypic data; polygenic risk score; population stratification; psychiatric genomics; rare variant; recruit; resilience; risk sharing; risk variant; success; symptom cluster; trauma exposure; traumatic event

Project Summary Psychiatric Genomics Consortium for PTSD Post-traumatic stress disorder (PTSD) occurs only in vulnerable individuals after exposure to severe traumatic events. This risk is due, in part, to 40-70% heritability of differential vulnerability or resilience. In fact, recent studies have suggested that the heritability for PTSD may be twice that of Major Depressive Disorder. Due to increasing collaborations across the field of PTSD genomics, it is a very exciting time for discovering the underlying genetic risk factors contributing to PTSD. The purpose of this application is to facilitate meta- analyses of genome-wide association study (GWAS) data for symptoms and diagnosis of PTSD. We propose to conduct this first large-scale meta-analysis through the PTSD group of the Psychiatric Genomics Consortium (PGC). The PGC was created in 2007 to conduct field-wide mega-analyses of individual data for five major psychiatric disorders. It united the field for the first time, and it is the largest consortium (>500 scientists from >80 institutions in 25 countries) in the history of psychiatry. The PGC has already produced three major findings with regard to the genetic architecture of psychiatric disorders. First, reliable associations can be identified with extremely large sample sizes. A meta-analysis of GWAS in SCZ has produced over 100 loci at the genome-wide significance threshold in a sample of 36,000 cases and 43,000 controls. Second, the polygenic architecture inferred from family studies was confirmed with molecular evidence, and refined via demonstration of substantial effects of both common and rare variants. Third, confirming findings from twin studies, there are shared genetic contributions among psychiatric disorders. The PGC-PTSD group was launched in May 2013 and since then has been enormously successful, with over 25 investigators contributing genotype data from over 20 studies with a total N of over 76,000 combined cases and trauma-exposed controls. We also have commitments of collaborations using ~ 77,000 additional cases and controls from banked samples from over 20 studies, and our progress thus far demonstrates feasibility of the proposed work. We hypothesize that with well-powered, large sample-size studies, along with a deeply phenotyped set of cohorts, the PGC-PTSD group can identify the genetic architecture of PTSD. We will test this hypothesis through our Primary Aim focusing on detecting novel genetic variation associated with risk for PTSD. The primary aim of this study is to detect novel genetic variants (SNPs and CNVs) that predict the development of PTSD following trauma. We will conduct the study in three stages – discovery, biological annotation, and replication. This aim will be supplemented by Exploratory Aims which will expand the genomic approaches to include GxE analyses, meta-analyses of intermediate phenotypes, and cross disorder polygenic risk score analyses. Identifying the genetic pathways underlying PTSD will lead to an improved neurobiological understanding, enhanced prevention, and improved treatment of this debilitating and prevalent syndrome.

项目摘要 PTSD的精神病基因组学联盟 创伤后应激障碍（PTSD）仅在暴露于严重的人后才发生 创伤事件。这种风险部分归因于差异脆弱性或韧性的40-70％的遗传力。实际上， 最近的研究表明，PTSD的遗传力可能是主要抑郁症的两倍。 由于PTSD基因组学领域的合作越来越高，这是一个非常激动人心的时刻 导致PTSD的潜在遗传危险因素。本应用的目的是促进元 全基因组关联研究（GWAS）数据的分析数据和PTSD诊断。 我们建议通过精神病学的PTSD组进行第一个大规模的荟萃分析 基因组学联盟（PGC）。 PGC成立于2007年，以进行范围内的个人大型分析 五种主要精神疾病的数据。它首次团结了领域，它是最大的财团 （在25个国家 /地区的80个机构中的500名科学家）在精神病学史上。 PGC已经 关于精神疾病的遗传结构产生了三个主要发现。首先，可靠 可以用极大的样本量来识别关联。 SCZ中GWAS的荟萃分析具有 在36,000例和43,000例样本中，在全基因组显着性阈值下产生了100多个基因座 控件。其次，用分子证实了从家庭研究推断出的多基因结构 证据，并通过证明共同变体和稀有变体的实质影响来进行完善。第三， 确认双胞胎研究的发现，精神疾病之间存在共同的遗传贡献。这 PGC-PTSD集团于2013年5月成立，此后取得了巨大成功，超过25 研究人员从20多个研究中贡献了基因型数据，共有76,000多个合并案例 和暴露于创伤的对照。我们还使用约77,000个案例有合作的承诺 以及来自20多个研究的银行样本的控制，到目前为止，我们的进展表明 拟议的工作。 我们假设，通过功能强大的大型研究，以及一组深厚的表型 同类PGC-PTSD组可以识别PTSD的遗传结构。我们将检验这个假设 通过我们的主要目的，重点是检测与PTSD风险相关的新遗传变异。 这项研究的主要目的是检测预测的新遗传变异（SNP和CNV） 创伤后的PTSD。我们将在三个阶段进行研究 - 发现，生物学注释和 复制。探索目的将补充此目标，该目标将扩大基因组方法 包括GXE分析，中间表型的荟萃分析和跨疾病多基因风险评分 分析。识别PTSD的遗传途径将导致改善的神经生物学 理解，增强预防并改善对这种衰弱和普遍综合征的治疗。