The role of genes and environment in anxiety spectrum disorders

基因和环境在焦虑谱系障碍中的作用

• 批准号: 8054216
• 负责人: JOHN M HETTEMA
• 金额: $ 50.8万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8054216
• 关键词: Accounting; Anxiety; Anxiety Disorders; Behavior; Bioinformatics; Candidate Disease Gene; Childhood; Chronic; Data; Data Analyses; Data Set; Data Sources; Depressive disorder; Development; Disease; Distress; Environment; Environmental Exposure; Environmental Risk Factor; Event; Exposure to; Fright; Functional disorder; Funding; Genes; Genetic; Genetic Determinism; Human; Impairment; Individual; International; Investigation; Life; Major Depressive Disorder; Measures; Medical; Mental disorders; Meta-Analysis; Methods; Modeling; Molecular Genetics; Mood Disorders; Mus; Neurotic Disorders; Patients; Personality Traits; Phenotype; Play; Population; Predisposition; Prevention; Prevention Research; Psychopathology; Research; Research Personnel; Risk; Rodent; Role; Sampling; Scheme; Schizophrenia; Source; Stress; Susceptibility Gene; Syndrome; Temperament; Testing; Twin Multiple Birth; Validation; Variant; Virginia; Weight; base; design; environmental stressor; follow-up; gene discovery; genetic association; genetic risk factor; genome wide association study; genome-wide; genome-wide linkage; human subject; novel; public health relevance; standard care

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.

描述（由申请人提供）：焦虑症在人群中非常普遍，并带来了显着的痛苦和损害负担。只有中等比例的焦虑症患者对当前的治疗有充分的反应，而且与其他精神综合征相比，焦虑症的研究相对不足。探索其遗传决定因素将有助于阐明其原因，并指导预防和新治疗方法的研究。研究已经记录了遗传因素（可能与抑郁症和焦虑气质共享）和暴露于环境压力源在焦虑症发展中的作用。然而，大多数分子遗传学研究在分析中没有考虑这些因素。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个候选的焦虑症易感基因，并通过其他人类和啮齿动物遗传学研究的证据进行加权。我们将测试这些基因和环境风险因素（如童年逆境和压力生活事件）的主要和交互作用，以确定它们在几个大型独立样本中的焦虑谱表型中的作用。 公共卫生相关性：焦虑症是相当常见的，慢性的，致残的。许多患有这些疾病的患者对标准治疗的耐受性差或反应不充分。遗传因素和暴露于环境压力都有助于其发展。鉴定在其易感性中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。