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

创伤后应激障碍 (PTSD) 性染色体 GWAS

基本信息

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
项目类别：
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

项目摘要

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.

项目概要在美国，未经治疗的创伤后应激障碍（PTSD）负担是导致民用和军事部门的医疗保健预算以及更好的治疗和预防方法需要最有力的预测因素之一，来预测谁会患上某种特定的精神疾病——包括。 PTSD – 女性被诊断患有创伤后应激障碍 (PTSD)、抑郁症、饮食。男性离线的频率大约是男性的两到三倍。在精神病学中，被诊断患有自闭症和药物滥用障碍的可能性高达四倍。很少有因素能够可靠地赋予风险倍数变化差异，但性别差异是一个例外。值得注意的是，PTSD 和其他疾病患病率存在性别差异的原因仍然相对较少。大规模遗传学研究，例如全基因组关联研究（GWAS），已经无法解释。然而，遗传对创伤后应激障碍（PTSD）和其他精神疾病的影响存在显着差距。文献中几乎所有主要的精神病学 GWAS 都遗漏了 X 和 Y 染色体。大型代表性 PTSD 样本的性染色体 GWAS 是迈向这一目标的关键第一步在我们之前的工作主导分析的基础上，将性染色体纳入所有主要的精神病学 GWAS 中。对于国际团体，我们将实施强大的性染色体分析管道，这将扩大这项工作还将提供必要的分析工作流程和为未来所有主要精神疾病的性染色体 GWAS 领域进行合作。关于性染色体对精神疾病的影响完全一无所知，至关重要的是我们确定性染色体位点并测试性染色体对遗传风险的不成比例的贡献针对创伤后应激障碍（PTSD）和抑郁症等疾病，以发现有关疾病病因学的新线索。可能有助于很好地解释精神疾病患病率和性染色体方面已知的性别差异研究结果可能对制定这些使人衰弱的治疗和预防策略至关重要和昂贵的疾病。