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

指控研究：遗传和环境带来的儿童自闭症风险

• 批准号: 7901226
• 负责人: Irva Hertz-Picciotto
• 金额: $ 40.57万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-03 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7901226
• 关键词: Address; Affect; Assisted Reproductive Technology; Autistic Disorder; Behavior; Behavioral; Biochemical Markers; Blood; Blood specimen; Body Burden; Characteristics; Charge; Child; Childhood; Clinic; Communication; Conceptions; Data Collection; Dental Amalgam; Development; Developmental Delay Disorders; Diet; Disease; Enrollment; Ensure; Environment; Environmental Exposure; Environmental Health; Environmental Risk Factor; Epidemiologic Studies; Exposure to; Fever; Flame Retardants; Funding; GSTM1 gene; General Population; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Risk; Goals; Home environment; Immune; Immune system; Immunologics; Immunophenotyping; Infection; Inflammatory Response; Institutes; Interview; Investigation; Language; Life; Low Prevalence; Maternal Exposure; Measures; Medical; Medical Records; Metabolism; Metal exposure; Metals; Mind; National Institute of Environmental Health Sciences; Neurodevelopmental Disorder; Newborn Infant; Nose; Parents; Participant; Pathogenesis; Pattern; Perinatal; Pesticides; Pharmaceutical Preparations; Phenotype; Play; Pregnancy; Pregnancy Complications; Prevalence; Protocols documentation; Public Health; Pyrethrins; Regulation; Reporting; Research; Research Personnel; Research Project Grants; Risk; Risk Factors; Role; Sample Size; Self Care; Social Interaction; Specificity; Spottings; Subgroup; Time; Vaccines; Work; Writing; Xenobiotic Metabolism; Xenobiotics; abstracting; base; case control; cognitive function; commercial application; cost; developmental disease; drug metabolism; early childhood; early onset; falls; fipronil; gene environment interaction; gene interaction; genetic profiling; interest; metal metabolism; neurodevelopment; pesticide exposure; phenyl ether; population based; prenatal; programs; skills; urinary

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.

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交流中的缺陷以及刻板印象或重复的行为或限制利益。尽管遗传学有很大的影响，但环境因素可能对许多儿童发挥因果作用。该疾病纯粹是由行为表型定义的，现在研究仅在生物学机制和发病机理的生化标志物上开始研究。拟议的项目将继续对自闭症的环境和遗传原因的流行病学研究，该研究由UC戴维斯戴维斯（UC Davis）环境卫生中心（CCEH）（CCEH）于2001年秋季由NIEHS（1 P01 ES11269），美国EPA和M.I.N.D. （神经发育障碍的医学调查）研究所。该项目被称为指控（遗传学和环境的儿童自闭症风险）研究，是对自闭症和回归触发因素的基本原因的全面，基于人群的病例对照研究。病例是自闭症儿童，还有另外两个组：发育迟缓的儿童和从普通人群中随机选择的儿童。到CCEH的第一个融资期结束时，将接近700名参与者。 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.拟议的研究将探讨暴露在孕妇周围，妊娠，围产期和幼儿期间的可能作用，包括感染，辅助生殖技术，药物，农药，溴化火焰阻燃剂和金属。它还将与涉及异种代谢的基因一起评估这些环境因素，或者由我们当前的微阵列结果或SNP阵列提出。最后，由于自闭症在异质表型中表现出来，因此我们将检查与自闭症特定亚型相关的所有暴露，这些自闭症是由发育模式定义的，例如回归与早期发作，高潮对。低自适应/认知功能，并通过免疫学特征。该项目解决了一个至关重要的公共健康问题，即自闭症；这种疾病影响到166名儿童中的多数。我们的项目将评估可能发挥因果作用的风险因素。