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

焦虑谱表型的全基因组关联研究：进一步推进 PGC 焦虑症工作组

基本信息

批准号：
9366044
负责人：
JOHN M HETTEMA
金额：
$ 38.12万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2021-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9366044
关键词：
Anxiety Anxiety Disorders Architecture Awareness Biological Chronic Comorbidity Complex Computer Simulation Data Depressive disorder Development Diagnostic Disease Distress Elements Environmental Risk Factor European Exposure to Family Functional disorder Generalized Anxiety Disorder Genes Genetic Genetic Determinism Genetic Research Genetic Risk Genetic screening method Genetic study Genomics Heritability Heterogeneity Human Genome Impairment Intervention Knowledge Major Depressive Disorder Measures Medical Mental Depression Mental disorders Meta-Analysis Methodology Modeling Molecular Genetics Mood Disorders National Institute of Mental Health Negative Finding Panic Disorder Pathologic Patients Phenotype Phobias Play Population Positioning Attribute Prevention Prevention Research Reporting Research Research Domain Criteria Residual state Risk Role Sample Size Sampling Schizophrenia Source Strategic Planning Stress Structure Suggestion Susceptibility Gene Syndrome Testing Time Validation Variant anxiety spectrum disorders anxious temperament base case control cohort design gene discovery genetic analysis genetic association genetic risk factor genetic variant genome wide association study genome-wide insight lifetime risk novel psychogenetics risk sharing risk variant success working group

项目摘要

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.

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，并带来重大的痛苦负担，损伤只有中等比例的焦虑症患者有反应目前的治疗干预措施，焦虑症是相对与其他精神病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，并指导预防和新的治疗。研究已经记录了遗传风险因素在发展中的作用焦虑症，其中许多是与其他内在表型，抑郁和焦虑气质（“焦虑谱”）。我们进行了一次在大约18，000名受试者中进行的初步全基因组关联研究（GWAS）使用新的表型方法对焦虑症进行了充分表征，捕捉遗传风险的共同来源。我们发现了几个全基因组显著的区域和与这些表型相关的多基因风险变异。的目的本申请是为了促进焦虑症的扩展GWAS。我们将在超过10万名受试者的数据中进行GWAS，分析共享与疾病特异性遗传风险，并扩大表型，包括抑郁症精神障碍和焦虑的气质。精神病基因组学联盟（PGC）在精神疾病的GWAS方面取得了巨大进展，但他们并没有因此主要集中在主AD上。最近建立的PGC焦虑症工作组将极大地促进该项目目标的实现，精神病遗传学研究的重大空白。这项研究将提供新的见解，焦虑谱系障碍发展的遗传机制。