Component A: CADDRE: Study to Explore Early Development (SEED) 3

项目摘要 自闭症谱系障碍(ASD)是一种神经发育障碍，可导致严重的终生障碍 对于受影响的个人。世界范围内ASD患病率的增加已经被记录在案，这已经 重大公共卫生影响，因为需要大量的家庭和社会资源来提供 为受影响的人提供长期服务。关于ASD的病因还有很多有待发现， 包括其发生和表现的风险和保护因素，以及有关表型变异 以及这些情况如何相互作用，在受ASD影响的人中。为了应对日益增长的公众 关于健康问题，2000年《儿童健康法》要求疾控中心建立自闭症监测和研究 针对自闭症和相关发育障碍的规模、发生率和原因的计划。 自闭症和发育障碍研究和流行病学中心(CADDRE)是 在六个国家(加利福尼亚州、科罗拉多州、佐治亚州、马里兰州、北卡罗来纳州和宾夕法尼亚州)建立，以 履行这项任务，目前正在进行研究的第二阶段，以探索早期发展 (SEED)，一项以人群为基础的病例对照研究。SEED的目标是检查ASD的表型 变异，包括核心症状的聚集、认知状态和共病的存在；遗传 变异和基因-环境相互作用(GxE)；以及感染、免疫功能、自身免疫、激素 可能影响ASD发生或表现的因素和母亲的生殖特征。数据 对种子的收集包括通过标准化工具和前期和 通过访谈、病历审查、自填式问卷和 生物样本。截至2015年12月，SEED 1和SEED 2已完成对4652个家庭--1341个家庭的数据收集 患有自闭症的有1722人，有其他发育障碍的有1722人，普通人群对照有1589人。这项建议 寻求实施SEED 3，每个研究组再招收625名儿童。合并后的更大 样本量将使种子假设的评估变得更加有力，特别是对表型亚群 和GxE交互作用。考虑到科罗拉多州和其他CADDRE站点的基础设施，以及他们的 成功实施SEED 1和SEED 2、SEED 3的丰富经验可在科罗拉多州快速实施 在整个网络中，创建临床、风险因素和生物学的组合种子样本 6500多个家庭的标本和数据。Seed将是同类ASD研究中规模最大的，使 对我们理解复杂的自闭症表型和识别潜在风险有重大贡献 以及ASD的保护因素，为未来干预和治疗的发展提供信息。

Project Summary Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that can cause severe lifelong impairment for affected individuals. An increase in the prevalence of ASD has been documented worldwide, which has major public health implications because of the substantial familial and societal resources required to provide long-term services to those who are affected. Much remains to be discovered about the causes of ASD, including risk and protective factors for its occurrence and presentation, as well as about phenotypic variations and co-occurring conditions, and how these interact, in persons affected by ASD. In response to growing public health concerns, the Children's Health Act of 2000 mandated CDC to establish ASD surveillance and research programs that address the magnitude, incidence, and causes of ASD and related developmental disabilities. The Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDREs) were established at six national sites (California, Colorado, Georgia, Maryland, North Carolina, and Pennsylvania) to fulfill this mandate and are currently carrying out the second phase of the Study to Explore Early Development (SEED), a population-based case-control study. The objectives of SEED are to examine ASD phenotypic variation, including clustering of core symptoms, cognitive status, and presence of co-morbidities; genetic variation and gene-environment interaction (GxE); and infection, immune function, autoimmunity, hormonal factors and maternal reproductive characteristics that may influence ASD occurrence or presentation. Data collection for SEED includes assessments of development through standardized instruments and pre- and perinatal health and environment via interviews, medical record review, self-administered questionnaires, and biologic samples. As of December 2015, SEED 1 & 2 had completed data collection on 4652 families - 1341 with ASD, 1722 with other developmental disorders, and 1589 general population controls. This proposal seeks to carry out SEED 3, enrolling 625 additional children in each study group. The combined greater sample size will enable well-powered assessment of SEED hypotheses, particularly for phenotypic subgroups and GxE interactions. Given the infrastructure in place at Colorado and the other CADDRE sites, and their extensive experience successfully implementing SEED 1 & 2, SEED 3 can be quickly implemented in Colorado and throughout the network, creating a combined SEED sample of clinical, risk factor, and biological specimens and data on over 6500 families. SEED will be the largest study of ASD of its kind, making significant contributions to our understanding of the complex autism phenotype and identifying potential risk and protective factors for ASD to inform future development of interventions and treatments.