Sex Chromosome GWAS of Post-Traumatic Stress Disorder (PTSD)

创伤后应激障碍 (PTSD) 性染色体 GWAS

• 批准号: 10453583
• 负责人: Laramie Duncan
• 金额: $ 23.45万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-19 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10453583
• 关键词: Adult; Anxiety Disorders; Biological; Budgets; Chromosomes; Collaborations; Data; Data Aggregation; Development; Diagnosis; Disease; Eating Disorders; Etiology; Familiarity; Female; Future; Gender; Genes; Genetic; Genetic Risk; Genetic study; Genotype; Healthcare; Heritability; International; Length; Link; Literature; Mental Depression; Mental disorders; Meta-Analysis; Methods; Military Personnel; Molecular Genetics; Post-Traumatic Stress Disorders; Prevalence; Prevention; Prevention strategy; Procedures; Protocols documentation; Pseudoautosomal Region; Psychiatry; Reporting; Resources; Risk; Sampling; Sex Chromosomes; Sex Differences; Substance Use Disorder; Testing; Time; Twin Studies; United States; Variant; Woman; Work; X Chromosome; Y Chromosome; autism spectrum disorder; base; cost; disorder risk; genome wide association study; genomic data; male; men; novel; psychiatric genomics; public health relevance; sex; substance use; success; therapy development; treatment strategy

Project summary The untreated burden of post-traumatic stress disorder (PTSD) in the United States is a massive contributor to healthcare budgets in both the civilian and military sectors, and better treatment and prevention methods are needed. One of the most powerful predictors of who will develop a particular psychiatric disorder – including PTSD – is sex/gender. Women are diagnosed with post-traumatic stress disorder (PTSD), depression, eating disorders, and certain anxiety disorders approximately two to three times as often as men. Conversely, males are up to four times more likely to be diagnosed with autism and substance use disorders. In psychiatry, there are few factors that reliably confer fold-change differences in risk, but sex differences are an exception. Remarkably, the reasons for sex differences in prevalence of PTSD and other disorders remain relatively unexplained. Large-scale genetic studies, such as genome-wide association studies (GWAS), have demonstrated genetic effects on PTSD and other psychiatric disorders. However, a notable gap in the literature is the omission of the X and Y chromosomes from nearly all major psychiatric GWAS. Here we propose sex chromosome GWAS of large representative PTSD samples as a critical first step towards the inclusion of sex chromosomes in all major psychiatric GWAS. Building upon our prior work leading analyses for international groups, we will implement robust pipelines for sex chromosome analyses, which will expand sex chromosome analysis to PTSD. This work will also provide the necessary analytic workflows and collaboration building for future sex chromosome GWAS of all major psychiatric disorders. The field is almost completely in the dark regarding sex-chromosome contributions to psychiatric disorders, and it is critical that we identify sex chromosome loci and test for disproportionate contributions of sex chromosomes to genetic risk for disorders like PTSD and depression, in order to discover novel clues about disease etiology. This work may help to explain well-known sex differences in prevalence of psychiatric disorders, and sex chromosome findings may prove critical for the development of treatment and preventative strategies for these debilitating and costly disorders.

项目总结 美国未经治疗的创伤后应激障碍(PTSD)负担是导致 民事和军事部门的保健预算，以及更好的治疗和预防方法 需要的。对谁会患上某种特定的精神障碍的最有力的预测因素之一--包括 创伤后应激障碍-是性/性别。女性被诊断为创伤后应激障碍(PTSD)、抑郁、进食 精神障碍和某些焦虑症的发病率大约是男性的两到三倍。相反，男性 被诊断为自闭症和物质使用障碍的可能性高出四倍。在精神病学中，有 几乎没有几个因素可以可靠地赋予折叠式变化风险差异，但性别差异是一个例外。 值得注意的是，创伤后应激障碍和其他疾病患病率存在性别差异的原因仍然相对较多 无法解释。大规模的遗传研究，如全基因组关联研究(GWAS)，已经 证明了基因对创伤后应激障碍和其他精神疾病的影响。然而，一个值得注意的差距是 文学是对几乎所有主要精神病学领域的X和Y染色体的省略。在这里我们 建议对具有代表性的创伤后应激障碍大样本进行性染色体GWA，作为迈向 将性染色体包括在所有主要的精神病学GWA中。在我们先前工作的基础上进行领先分析 对于国际组织，我们将实施强大的性染色体分析管道，这将扩大 性染色体分析对创伤后应激障碍的影响。这项工作还将提供必要的分析工作流程和 为所有主要精神疾病的未来性染色体建立合作关系。田野几乎是 关于性染色体对精神疾病的贡献是完全不知道的，关键是 我们确定了性染色体基因座，并测试了性染色体对遗传风险的不成比例贡献。 对于像创伤后应激障碍和抑郁症这样的疾病，以发现关于疾病病因的新线索。这部作品 可能有助于解释众所周知的精神障碍患病率的性别差异，以及性染色体 这些发现可能被证明对开发治疗和预防这些衰弱的策略至关重要。 以及代价高昂的疾病。