Gene-Environment Interplay, Development, and Emotional Disorders

基因-环境相互作用、发育和情绪障碍

• 批准号: 7690959
• 负责人: William Copeland
• 金额: $ 14.37万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-23 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7690959
• 关键词: 21 year old; Academic Medical Centers; Address; Adolescence; Affect; African American; Age; American Indians; Anxiety; Anxiety Disorders; Biological; Brain-Derived Neurotrophic Factor; Candidate Disease Gene; Categories; Child; Childhood; Chronic; Cognitive; Comorbidity; Complex; Consultations; Data; Depressive disorder; Development; Educational Curriculum; Emotional disorder; Environment; Environmental Risk Factor; Epidemiology; Ethical Issues; Ethnic group; Etiology; Event; Foundations; Funding; Genes; Genetic; Genetic Markers; Genetic Risk; Genomics; Goals; HTR2A gene; Individual; Intervention; Life; Measures; Mediator of activation protein; Mental Health; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentors; Meta-Analysis; Methaqualone; Minisatellite Repeats; Modeling; Molecular; Molecular Genetics; Neurobiology; O-(glucuronic acid 2-sulfate)-(1--4)-O-(2,5)-anhydromannitol 6-sulfate; Outcome; Phenotype; Population; Preparation; Prevention; Psychopathology; Public Health; Publications; Publishing; Recruitment Activity; Research; Research Personnel; Research Training; Risk; Sampling; Staging; Stress; Stressful Event; Subgroup; Symptoms; Testing; Time; Training; Training Programs; Variant; Work; aged; base; career; cooking; data sharing; depression; depressive symptoms; design; ethical legal social implication; falls; follow-up; gene environment interaction; genome wide association study; genome-wide; high risk; member; novel marker; population based; programs; racial and ethnic; response; skills; stressor

DESCRIPTION (provided by applicant): The purpose of this Mentored Patient-Oriented Research Career Development Award (K23) is to enable the candidate to become an independent researcher investigating genetic contributions to developmental psychopathology under conditions of adversity. The research goal is to study the pleiomorphic psychopathologic expression of promising genetic markers under varying conditions of adversity across childhood and adolescence. To prepare for this research, the training program focuses on integrating skills in developmental epidemiology with molecular genetics, statistical genetics, and ethical, legal, and social issues. This training will include working directly with Drs. Costello and Sullivan on two GWAS projects. The candidate is based in the Center for Developmental Epidemiology, Duke University Medical Center. Sponsors include Jane Costello PhD (developmental psychopathology and comorbidity), Patrick Sullivan MD FRANZCP (psychiatric geneticist), David Goldstein, PhD (population and molecular geneticist), Elizabeth Mauser, PhD (statistical geneticist), and Robert Cook-Deegan, MD (ethical, legal, and social issues of genetics and genomics). The research plan proposes to study gene-environment interaction models for (1) promising genetic markers include HTTLPR, HTR2A T102C, MAOA-u VNTR, BDNF va!66met and COMT val158met and additional markers identified based upon the results of psychiatric GWAS studies, (2) four environment risk categories (i.e., negative life events, potentially traumatic events, chronic stressors, and empirically-derived adversity profiles), (3) two outcomes (i.e., anxiety and depressive symptoms), and (4) two developmental periods (i.e., childhood and adolescence). Hypotheses will be tested in a population-based sample of children (CCC study; 1627 assessments of 920 subjects aged 9-17) and then retested in another longitudinal sample (GSMS study; 8804 assessments of 1420 subjects aged 9-21, up to 10 assessments per subject). The application will also support preparation and submission by the investigator of an R01 application following up with vulnerable subgroups identified in the current analysis to study neurobiological mediators of genetic risk. This work provides a framework for unpacking the complex expression of genetic risk in response to environmental and developmental variations. Identifying high-risk groups can inform prevention and treatment interventions and our understanding of the etiology of childhood psychopathology.

描述（由申请人提供）：该以患者为导向的研究职业发展奖（K23）的目的是使候选人成为一名独立研究人员，研究逆境条件下基因对发展性精神病理学的贡献。研究目标是研究有希望的遗传标记在童年和青春期不同逆境条件下的多形性精神病理学表达。为了准备这项研究，培训计划侧重于将发展流行病学技能与分子遗传学、统计遗传学以及伦理、法律和社会问题相结合。该培训将包括直接与博士合作。 Costello 和 Sullivan 参与两个 GWAS 项目。该候选人位于杜克大学医学中心发展流行病学中心。 赞助商包括 Jane Costello 博士（发展精神病理学和合并症）、Patrick Sullivan MD FRANZCP（精神遗传学家）、David Goldstein 博士（人口和分子遗传学家）、Elizabeth Mauser 博士（统计遗传学家）和 Robert Cook-Deegan 医学博士（伦理学） 、遗传学和基因组学的法律和社会问题）。该研究计划建议研究基因-环境相互作用模型：(1) 有前景的遗传标记包括 HTTLPR、HTR2A T102C、MAOA-u VNTR、BDNF va!66met 和 COMT val158met 以及根据精神病学 GWAS 研究结果确定的其他标记，(2) 四种环境风险类别（即负面生活事件、潜在的创伤性事件）事件、慢性压力源和经验得出的逆境概况），（3）两种结果（即焦虑和抑郁症状），以及（4）两个发育时期（即儿童期和青春期）。假设将在基于人群的儿童样本中进行检验（CCC 研究；对 920 名 9-17 岁受试者进行 1627 次评估），然后在另一个纵向样本中重新测试（GSMS 研究；对 1420 名 9-21 岁受试者（最多 10 名）进行 8804 次评估）每个科目的评估）。该申请还将支持研究人员准备和提交 R01 申请，跟踪当前分析中确定的弱势亚群，以研究遗传风险的神经生物学介质。这项工作提供了一个框架，用于解析遗传风险响应环境和发育变化的复杂表达。识别高危人群可以为预防和治疗干预措施以及我们对儿童精神病理学病因的理解提供信息。