Gene-Environment Interactions in an Autism Birth Cohort

自闭症出生队列中的基因与环境相互作用

• 批准号: 6805581
• 负责人: W. Ian Lipkin
• 金额: $ 247.71万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6805581
• 关键词: active immunization; autism; autoimmune disorder; biomarker; blood chemistry; clinical research; cooperative study; developmental neurobiology; disease /disorder etiology; environmental exposure; family genetics; gene environment interaction; genetic disorder diagnosis; genetic susceptibility; genotype; high throughput technology; human genetic material tag; human subject; infection; interview; longitudinal human study; low birth weight infant human; mental disorder diagnosis; mental health epidemiology; methylmercury; neuropsychology; neurotoxins; pathologic process; polymerase chain reaction; proteomics; questionnaires; statistics /biometry

Reports of increasing prevalence of autism spectrum disorders (ASDs), a set of highly genetic conditions, are intensifying interest in the role of environmental exposures, including infectious, immune, and toxic factors. Retrospective studies exploring associations between environmental factors and ASDs are compromised by selection bias, small sample sizes, possibly invalid diagnosis, and absence of biologic measures. This prospective study will employ an unselected birth cohort of 75,500 in which cases are ascertained through screening of the entire population, diagnoses established using uniform procedures, extensive histories and clinical data obtained, and biologic samples collected serially throughout pregnancy and early childhood. The application of high throughput laboratory assays to derive maximal information from developmentally-influenced, finite, and nonrenewable biologic samples, and inclusion of early screening and diagnostic assessments, will permit an unprecedented, rich view of the longitudinal trajectory and nascent signs and symptoms of ASDs, facilitate discovery of biomarkers, and afford unique insights into the role of gene:environment interactions in ASD pathogenesis. Specific aims are to: (1) establish the Autism Birth Cohort (ABC) through ascertainment of cases of autism spectrum disorder (ASD, N=150-233) and selection of controls (N-1000) from the Norway Mothers and Child (MoBa) cohort; (2) examine biologic pathways that may predispose to ASD, through evaluation of immune, endocrine, and neuroregulatory factors in mothers during early gestation or at birth and in children, at birth or 30 months postnatal; (3) identify environmental factors that may be directly or indirectly associated with ASD, including pre- or postnatal infection, vaccination, very low birth weight or other obstetric risk factors in which infections are implicated, dietary and/or environmental exposure to methylmercury; (4) describe the natural history of clinical, anthropometric, and neurobehavioral features of ASD; and (5) explore genotypic influences that may be directly or indirectly associated with ASD by testing associations of ASD and/or its endophenotypes with family history of autoimmune disease or selected candidate genes, and investigating conditional gene-environment effects using antecedent factors found to influence ASD risk.

自闭症谱系障碍（ASD）是一组高度遗传的疾病，其患病率不断增加，这引起了人们对环境暴露（包括传染性、免疫性和毒性因素）的作用的兴趣。探索环境因素与自闭症谱系障碍之间关联的回顾性研究因选择偏倚、样本量小、诊断可能无效以及缺乏生物学措施而受到损害。这项前瞻性研究将采用未经选择的 75,500 名出生队列，通过对整个人群进行筛查、使用统一程序进行诊断、获得广泛的病史和临​​床数据以及在整个怀孕和幼儿期连续收集的生物样本来确定病例。应用高通量实验室检测来从中获取最大信息 受发育影响的、有限的、不可再生的生物样本，以及早期筛查和诊断评估，将能够对自闭症谱系障碍的纵向轨迹和新生体征和症状产生前所未有的、丰富的了解，促进生物标志物的发现，并提供对自闭症谱系障碍的独特见解。基因：环境相互作用在 ASD 发病机制中的作用。 具体目标是： (1) 通过查明自闭症谱系障碍 (ASD，N=150-233) 病例并从挪威母亲和儿童 (MoBa) 中选择对照 (N-1000)，建立自闭症出生队列 (ABC) ）队列； (2) 通过评估母亲在妊娠早期或出生时以及儿童、出生时或产后 30 个月的免疫、内分泌和神经调节因素，检查可能诱发 ASD 的生物途径； (3) 确定可能与 ASD 直接或间接相关的环境因素，包括产前或产后感染、疫苗接种、极低出生体重或其他涉及感染的产科危险因素、饮食和/或环境中甲基汞暴露； (4) 描述 ASD 的临床、人体测量和神经行为特征的自然史； (5) 通过测试 ASD 和/或其内表型与自身免疫性疾病家族史或选定候选基因的关联，探索可能与 ASD 直接或间接相关的基因型影响，并使用发现影响的先行因素研究条件基因-环境效应自闭症谱系障碍风险。