Genetic Epidemiology of Autism Spectrum Disorders

描述（由申请人提供）：候选人是一名儿童和青少年精神病学家和一名流行病学家，在分子遗传学，统计遗传学/生物信息学和自闭症方面接受过有限的培训，希望发展她在发展精神病理学和全基因组关联研究中进行独立遗传流行病学研究的能力。 这项建议的总体目标是发展遗传流行病学方面的专门知识， 跨学科的转化科学，结合流行病学，功能基因组学，分子遗传学，高通量基因分型，生物信息学和专门的计算方法。需要这种专业知识来帮助揭示疾病机制，并将获得的知识转化为自闭症谱系障碍（ASD）等复杂疾病的预防和干预措施。这些技能将通过与导师的密切关系以及精心策划的综合和接口课程和指导研究来获得和增强。 该提案的教育目标是通过教程和课程开发新的技能：1） 为研究群体遗传学建立一个概念框架（肯尼思·基德），罕见的遗传变异 疾病过程中的方法和遗传机制（马修状态）和常见的遗传变异 发展精神病理学方法（Edwin Cook）; 2）培养分析密集和复杂的遗传流行病学数据库的计算技能，并培养管理大量复杂的交互式遗传数据集的生物信息学技能了解ASD的表型、内表型、运动轨迹和神经生物学（弗雷德·埃克塞特马尔）; 4）通过检查其公共卫生意义及其对筛查、诊断和干预的影响，对拟议研究产生的知识应用转化科学方法（詹姆斯·莱克曼）。 研究建议包括与培训目标直接相关的三个具体目标：1）维持和扩大韩国流行病学队列（在一个具有遗传学和遗传学差异的韩国人群中），2）收集韩国样本的综合表型数据，和3）在两阶段关联研究设计中用内部复制样本测试三个候选基因的关联，这反过来将允许产生和测试关于ASD中基因-环境相互作用的假设。 这项建议利用了一个难得的机会，丰富了正在进行的研究，同时支持了一项 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.