The Charge Study: Childhood Autism Risks from Genetics and the Environment

描述（由申请人提供）：自闭症是一种严重的发育障碍，其特征是社会互动和沟通的缺陷，以及刻板或重复的行为或有限的兴趣。尽管遗传因素有很强的影响力，但环境因素可能对许多儿童起着因果作用。这种疾病纯粹是由行为表型定义的，现在才开始研究发病机制的生物学机制和生化标志物。拟议的项目将继续进行自闭症的环境和遗传原因的流行病学研究，该研究是在加州大学戴维斯分校儿童环境健康中心（CCEH）的资助下于2001年秋季开始的，由NIEHS（1 P01 ES 11269），美国EPA和M.I.N.D.神经发育障碍医学研究所（Medical Investigations of Neurodevelopmental Disorders）该项目被称为CHARGE（遗传学和环境造成的儿童自闭症风险）研究，是一项全面的、基于人群的病例对照研究，旨在研究自闭症的根本原因和消退的触发因素。案例是自闭症儿童，另外两组包括：发育迟缓的儿童和从普通人群中随机选择的儿童。到CCEH第一个资助期结束时，将有近700名参与者参加CHARGE。由于招募和数据收集的成本较高，CHARGE研究的拟议继续将使用R 01机制，该机制过于昂贵，无法在CCEH内维持，并将样本量扩大至1600例。较大的样本量将允许检查相对较低患病率的暴露、基因-环境相互作用以及由表型特征定义的自闭症亚型的病因特异性。拟议的研究将探讨围概念、妊娠、围产期和幼儿期接触的可能作用，包括感染、辅助生殖技术、药物、农药、溴化阻燃剂和金属。它也将评估这些环境因素与基因参与异生物质代谢或建议我们目前的微阵列结果或SNP阵列。最后，由于自闭症表现为异质性表型，我们将检查与自闭症特定亚型相关的所有暴露，这些亚型由发育模式定义，如退化与早发，高与低。低适应性/认知功能和免疫学特征。该项目针对的是一个日益严重的公共卫生问题，即自闭症;每166名儿童中就有一名患有自闭症。我们的项目将评估可能起因果作用的风险因素。

DESCRIPTION (provided by applicant): Autism is a severe developmental disorder characterized by deficits in social interaction and communication and by stereotypic or repetitive behaviors or restricted interests. Despite a strong influence of genetics, environmental factors are likely to play a causal role for many children. The disorder is defined purely by behavioral phenotype, with research only now burgeoning on biologic mechanisms and biochemical markers of pathogenesis. The proposed project will continue an epidemiologic study of the environmental and genetic causes of autism that was initiated under the UC Davis Center for Children's Environmental Health (CCEH) funded in the fall of 2001 by the NIEHS (1 P01 ES11269), U.S. EPA, and M.I.N.D. (Medical Investigations of Neurodevelopmental Disorders) Institute. This project, known as the CHARGE (Childhood Autism Risks from Genetics and Environment) Study, is a comprehensive, population-based case-control investigation of underlying causes for autism and triggers of regression. Cases are children with autism, and two other groups are included: children with developmental delay and children selected at random from the general population. Close to 700 participants will have been enrolled in CHARGE by the end of the first funding period of the CCEH. The proposed continuation of the CHARGE study will use the R01 mechanism due to the high cost of recruitment and data collection, which is too expensive to maintain within the CCEH, and will extend the sample size to 1600. The larger sample size will permit the examination of exposures of relatively low prevalence, of gene- environment interactions, and of etiologic specificity for subtypes of autism defined by phenotypic characteristics. The proposed study will address the possible role of exposures during the peri-conceptional, gestational, perinatal, and early childhood periods, including infections, assisted reproductive technology, medications, pesticides, brominated flame retardants, and metals. It will also evaluate these environmental factors in conjunction with genes involved in xenobiotic metabolism or suggested by our current microarray results or by SNP arrays. Finally, because autism manifests in heterogeneous phenotypes, we will examine all exposures in relation to specific subtypes of autism defined by developmental patterns such as regression versus early onset, high versus. low adaptive/cognitive function, and by immunologic profiles. This project addresses a critical and growing public health concern, namely, autism; this disorder affects as many as one in 166 children. Our project will evaluate risk factors that may play a causal role.