Genetic Epidemiology of Autism Spectrum Disorders

应聘者描述(由申请人提供)：应聘者是一名儿童和青少年精神病学家，也是一名流行病学家，在分子遗传学、统计遗传学/生物信息学和自闭症方面的培训有限，希望发展自己的能力，在发育精神病理学和全基因组研究中进行独立的遗传流行病学研究。 这项建议的总体目标是发展遗传流行病学方面的专业知识； 融合了流行病学、功能基因组学、分子遗传学、高通量基因分型、生物信息学和专业计算方法的跨学科转化学。需要这种专门知识来帮助揭示疾病机制，并将所获得的知识转化为对自闭症谱系障碍等复杂疾病的预防和干预。这些技能将通过与导师的密切关系以及精心规划的综合和相互联系的课程工作和指导研究来获得和增强。 这项建议的教育目标是通过教程和课程作业发展新的技能集：1) 开发一个研究群体遗传学的概念框架(Kenneth Kidd)，罕见的遗传变异 疾病过程中的途径和遗传机制(马太状态)和常见的遗传变异 (2)培养分析密集和复杂遗传流行病学数据库的计算技能，并开发生物信息学技能以管理海量、复杂的成套互动遗传数据(赵宏宇)；3)了解自闭症的表型、内表型、轨迹和神经生物学(Fred Volkmar)；以及4)对拟议研究产生的知识应用转化科学方法，研究其对公共卫生的意义及其对筛查、诊断和干预的影响(James Leckman)。 研究建议包括与培训目标直接相关的三个具体目标：1)维持和扩大已作为自闭症讲话者资助赠款的一部分建立的韩国流行病学队列(在患有自闭症和遗传缺陷的韩国人群中)，2)收集韩国样本的全面表型数据，以及3)在两阶段关联研究设计中测试三个候选基因与内部复制样本的相关性，这将反过来允许生成和测试关于自闭症基因与环境相互作用的假说。 这项建议利用了一个难得的机会来丰富正在进行的研究，同时支持 扩大申请人的研究技能和能力。

DESCRIPTION (provided by applicant): The candidate is a child and adolescent psychiatrist and an epidemiologist with limited training in molecular genetics, statistical genetics/bioinformatics and autism who wishes to develop her capacity to conduct independent genetic epidemiology research in developmental psychopathology and genome-wide association studies. The overall goal of this proposal is to develop expertise in genetic epidemiology; an integrated, interdisciplinary translational science that combines epidemiology, functional genomics, molecular genetics, high-throughput genotyping, bioinformatics and specialized computational methods. This expertise is needed to help uncover disease mechanisms and translate acquired knowledge to the prevention and interventions for complex diseases such as Autism Spectrum Disorder (ASD). These skills will be acquired and enhanced through close relationships with mentors and by carefully planned integrated and interfacing coursework and mentored research. Educational goals of this proposal are to develop new skill sets through tutorials and coursework: 1) to develop a conceptual framework for studying population genetics (Kenneth Kidd), rare genetic variant approach and genetic mechanisms in disease processes (Matthew State) and common genetic variant approach in developmental psychopathology (Edwin Cook); 2) to develop computational skills for analyzing intensive and complex genetic epidemiological databases and to develop bioinformatics skills for managing massive, complex sets of interactive genetic data (Hongyu Zhao); 3) to understand phenotype, endophenotype, trajectory and neurobiology of ASD (Fred Volkmar); and, 4) to apply a translational scientific approach to the knowledge generated from the proposed research by examining its public health significance and its implication for screening, diagnoses and intervention (James Leckman). The research proposal includes three specific aims relating directly to the training goals: 1) to maintain and expand the Korean epidemiological cohort (in an enthinically and genetically disctinictive Korean population) already established as a part of an Autism Speaks-funded grant, 2) to collect comprehensive phenotype data on the Korean sample, and 3) to test the association of three candidate genes in a two-stage association study design with an internal replication sample, which will in turn allow for generation and testing of hypotheses about gene-environment interactions in ASD. This proposal takes an advantages of a rare opportunity to enrich an ongoing study while supporting an expansion of the applicant's research skills and abilities.