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

项目摘要 在美国，未经治疗的创伤后应激障碍（PTSD）负担是导致 在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， needed.一个最有力的预测谁将发展一个特定的精神疾病-包括 PTSD -是性/性别。女性被诊断为创伤后应激障碍（PTSD），抑郁症，进食 焦虑症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， 有几个因素可靠地赋予倍数变化的风险差异，但性别差异是一个例外。 值得注意的是，PTSD和其他疾病患病率的性别差异的原因仍然相对 无法解释大规模的遗传学研究，如全基因组关联研究（GWAS）， 证明了遗传对创伤后应激障碍和其他精神疾病的影响。然而，一个明显的差距， 文献中的最大缺陷是几乎所有主要的精神病GWAS都遗漏了X和Y染色体。这里我们 提出性染色体GWAS的大型代表性PTSD样本作为关键的第一步， 包括性染色体在所有主要的精神病GWAS。基于我们之前的工作， 对于国际组织，我们将实施强有力的性染色体分析管道， 性染色体分析与创伤后应激障碍有关这项工作还将提供必要的分析工作流程， 为未来所有主要精神疾病的性染色体GWAS建立合作。该领域几乎是 关于性染色体对精神疾病的贡献，完全处于黑暗之中，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， 用于创伤后应激障碍和抑郁症等疾病，以发现疾病病因的新线索。这项工作 可能有助于解释众所周知的精神疾病患病率的性别差异，以及性染色体 这些发现可能对这些衰弱的治疗和预防策略的发展至关重要。 和昂贵的疾病。

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.