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沟通缺陷，以及刻板或重复的行为或限制的兴趣。尽管遗传因素的影响很大，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来定义的，目前对发病机制的生物学机制和生化标志物的研究才刚刚兴起。该项目将继续对自闭症的环境和遗传原因进行流行病学研究，该研究是由加州大学戴维斯分校儿童环境健康中心（CCEH）发起的，该中心于2001年秋季由NIEHS (1 P01 ES11269)，美国环保署和M.I.N.D.（神经发育障碍医学调查）研究所资助。这个项目被称为CHARGE（遗传和环境导致的儿童自闭症风险）研究，是一项全面的、以人群为基础的病例对照调查，旨在研究自闭症的潜在原因和退化的触发因素。病例包括自闭症儿童，另外两组包括：发育迟缓儿童和从一般人群中随机挑选的儿童。到CCEH的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太高，无法在CCEH内维持，因此建议继续进行CHARGE研究将使用R01机制，并将样本量扩大到1600人。更大的样本量将允许检查相对低患病率的暴露，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。拟议的研究将解决在围孕期、妊娠期、围产期和幼儿期暴露的可能作用，包括感染、辅助生殖技术、药物、杀虫剂、溴化阻燃剂和金属。它还将评估这些环境因素与参与外源代谢的基因，或由我们目前的微阵列结果或SNP阵列提示的基因。最后，由于自闭症表现为异质性表型，我们将检查所有与发育模式定义的特定亚型自闭症相关的暴露，如退行性与早发性，高水平与高水平。低适应/认知功能，免疫特征。该项目解决了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1名患有这种疾病。我们的项目将评估可能起因果作用的风险因素。