Genome-wide association studies of anxiety spectrum phenotypes: Furthering the PGC Anxiety Disorders Working Group

焦虑症，如广泛性焦虑症、恐慌症和恐惧症 在人群中高度流行，并带来巨大的痛苦和负担 减损。只有中等比例的焦虑症患者有反应 对目前的治疗干预措施足够，焦虑症相对 与其他精神病学综合征相比，研究不足。探索他们的基因 决定因素将有助于阐明其原因，并指导预防和新的研究 治疗。研究已经证明了遗传风险因素在发育中的作用。 焦虑症，其中许多与其他内在化表型相同，如 抑郁和焦虑的气质(“焦虑症”)。我们已经进行了一次 对大约18,000名受试者进行的初步全基因组关联研究 使用新的表型方法很好地表征了焦虑症 捕捉常见的遗传风险来源。我们发现了几个全基因组意义上的 与这些表型相关的区域和多基因风险变异。目的 目前这一应用是为了促进焦虑症的广泛性治疗。我们会 在来自100,000多名受试者的数据中进行GWA，分析共享与 疾病特有的遗传风险，并扩大表型以包括抑郁 精神障碍和焦虑的气质。精神病学基因组联盟(PGC)已经 在治疗精神障碍方面取得了巨大的进步，但他们并没有 Far专注于主要的广告。PGC焦虑症的最新建立 工作组将极大地促进本项目目标的实现，填写 精神病学遗传学研究方面的重大差距。这项研究将为 焦虑症发展的遗传机制。

Anxiety disorders such as generalized anxiety disorder, panic disorder, and phobias 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 treatment interventions, 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 genetic risk factors in the development of anxiety disorders, many of which are shared with other internalizing phenotypes like depression and anxious temperament (“anxiety-spectrum”). We had conducted a preliminary genome-wide association study (GWAS) in approximately 18,000 subjects well-characterized for anxiety disorders using novel phenotypic approaches designed to capture common sources of genetic risk. We identified several genome-wide significant regions and polygenic risk variation associated with these phenotypes. The purpose of this current application is to facilitate expanded GWAS of the anxiety disorders. We will conduct GWAS in data from over 100,000 subjects, dissect the effects of shared versus disorder-specific genetic risk, and expand the phenotypes to include depressive disorders and anxious temperament. The Psychiatric Genomics Consortium (PGC) has achieved enormous progress in GWAS of psychiatric disorders, but they have not thus far focused on the primary ADs. The recent establishment of the PGC Anxiety Disorders Working Group will greatly facilitate accomplishment of the aims of this project, filling a major gap in psychiatric genetics research. This study will provide new insights into genetic mechanisms underlying the development of anxiety-spectrum disorders.