The role of genes and environment in anxiety spectrum disorders

描述(由申请人提供)：焦虑症在人群中非常普遍，并带有明显的痛苦和损害负担。只有中等比例的焦虑症患者对目前的治疗方法有足够的反应，与其他精神综合征相比，焦虑症的研究相对较少。探索它们的遗传决定因素将有助于阐明它们的原因，并指导预防和新治疗的研究。研究已经证明了遗传因素和环境应激源在焦虑症发展中的作用，这两个因素很可能与抑郁障碍和焦虑气质相同。然而，大多数分子遗传学研究在他们的分析中没有考虑到这些因素。在这个项目中，我们将从全基因组关联分析中仔细选择10-15个候选焦虑症易感基因，并结合其他人类和啮齿动物遗传学研究的证据进行加权。我们将在几个大的、独立的受试者样本中测试这些基因和环境风险因素(如童年逆境和应激生活事件)在焦虑谱型中的作用的主要和交互作用。 公共卫生相关性：焦虑症是相当常见的、慢性的和致残的。许多患有这些疾病的患者要么耐受性差，要么对标准治疗没有足够的反应。遗传因素和暴露在环境压力下都有助于它们的发育。识别对其易感性起作用的基因将为其病因提供新的线索，并有望为预防和治疗研究提供新的方向。

DESCRIPTION (provided by applicant): Anxiety disorders are highly prevalent in the population and carry a significant burden of distress and impairment. Only a moderate proportion of patients with anxiety disorders respond adequately to current treatments, and anxiety disorders are relatively understudied compared to other psychiatric syndromes. Exploring their genetic determinants will help elucidate their causes and guide research for prevention and new treatments. Research has documented roles for both genetic factors, likely shared with depressive disorders and anxious temperament, and exposure to environmental stressors in the development of anxiety disorders. Yet most molecular genetic studies have not taken these factors into account in their analyses. In this project, we will carefully select 10-15 candidate anxiety disorder susceptibility genes from genome-wide association analyses weighted by evidence from other human and rodent genetic studies. We will test the main and interactive effects of these genes and environmental risk factors such as childhood adversity and stressful life events for their role in anxiety spectrum phenotypes in several large, independent samples of subjects. PUBLIC HEALTH RELEVANCE: The anxiety disorders are quite common, chronic, and disabling. Many patients with these conditions either poorly tolerate or do not adequately respond to standard treatments. Both genetic factors and exposure to environmental stress contribute to their development. The identification of the genes that play a role in their susceptibility will provide new clues to their causes and, hopefully, new directions for prevention and treatment research.