Project 1: Epidemiology and the Environment in Autism (Hertz-Picciotto)

项目 1：自闭症的流行病学和环境（Hertz-Picciotto）

• 批准号: 9288164
• 负责人: Irva Hertz-Picciotto
• 金额: $ 13.64万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9288164
• 关键词: Address; Agriculture; Ants; Autistic Disorder; Bioinformatics; Biological Markers; Case-Control Studies; Characteristics; Chemicals; Child; Child Development; Cognitive; Cohort Studies; Communities; Culicidae; DNA Methylation; Data; Data Sources; Development; Developmental Delay Disorders; Diagnosis; Dictyoptera; Enrollment; Environment; Epidemiology; Epigenetic Process; Exposure to; FRAP1 gene; Family history of; Flame Retardants; Fleas; Fogs; Food Packaging; Foundations; Gene Expression; Genes; Genetic; Genetic Polymorphism; Genetic Risk; Health; Household; Household Products; Human Milk; Immune; Immunologic Markers; Insecticides; Interview; Investigation; Language; Language Delays; Learning; Life Style; Link; Measurement; Measures; Medical Records; Modeling; Molecular Profiling; Mothers; Nutritional; Occupational Exposure; Outcome; Participant; Pathway interactions; Patient Self-Report; Pennsylvania; Pharmaceutical Preparations; Phenotype; Plasma; Pregnancy; Pregnant Women; Prevention strategy; Public Health; Questionnaires; Resources; Risk; Risk Factors; Siblings; Specimen; Speech; Textiles; Toxic effect; Toxicokinetics; Urine; autism spectrum disorder; base; case control; cytokine; disorder prevention; effective intervention; epidemiology study; epigenetic marker; fly; genetic variant; genomic profiles; high risk; immune function; immunological status; indexing; interest; modifiable risk; pet animal; phenome; polybrominated diphenyl ether; population based; pregnant; prospective; pyrethroid; urinary

Project 1, Epidemiology & Environment, will leverage existing resources from two large epidemiologic studies to address the potential contribution from several common household exposures to risk for an autism spectrum disorder (ASD), separately and in combination with certain genomic or epigenetic profiles. The two existing investigations are: the population-based case-control CHARGE (CWildhood Autism Risk from Genetics and Environment) Study, and MARBLES (Markers of Autism Risk in Babies�Learning Early Signs), a cohort study following pregnant women who previously delivered a child that developed autism to understand what influences the outcome of the younger sibling and to identify early markers of ASD. Chemical classes of interest for Project 1 are: polybrominated diphenyl ethers (PBDEs, used as flame retardants), their hydroxylated metabolites, perfluorinated compounds (PFCs, used as coatings on non-stick cookware, textiles, food packaging, etc.), and pyrethroid insecticides (used in sprays and foggers to control ants, cockroaches, flies and mosquitos, and on pets to control fleas). Chemical determinations made in Core C in various media (plasma, urine, breastmilk) will be supplemented by toxicokinetic modeling and exposures assessed by questionnaire and other data sources. These will be examined in relation to child's developmental status, i.e., ASD, developmental delay (DD), specific speech /language delay, and other trajectories, and for associations with markers of immune function generated in Project 3, and epigenetic markers from Project 2. Differential impact of the PBDEs, PFCs, and pyrethroids will be evaluated based on relevant genetic polymorphisms, CNVs, or measures of global DNA methylation, considering mechanistic pathways that link to these compounds. Finally, with the bio-informatics team at Pennsylvania State Univ, we will explore, in discovery-oriented mode, a wide array of exposures from biologic specimens, interviews, and medical records, along with the genetic and epigenetic data.

项目 1“流行病学与环境”将利用两项大型流行病学研究的现有资源，分别或结合某些现有的基因组或表观遗传学研究，探讨几种常见家庭暴露于自闭症谱系障碍 (ASD) 风险的潜在贡献。包括：基于人群的病例对照 CHARGE（来自遗传和环境的野生自闭症风险）研究和 MARBLES（婴儿学习早期迹象的自闭症风险标记）队列研究跟踪曾经生过患有自闭症孩子的孕妇，以了解影响弟弟妹妹结局的因素，并确定项目 1 感兴趣的化学类别：多溴二苯醚（PBDE，用作阻燃剂）、它们的羟基化代谢物、全氟化合物（PFC，用作不粘炊具、纺织品、食品包装等的涂层）和拟除虫菊酯杀虫剂（用于喷雾剂和喷雾器来控制蚂蚁、蟑螂、苍蝇和蚊子，以及在宠物上控制跳蚤），Core C 在各种介质（血浆、尿液、母乳）中进行的化学测定将通过毒代动力学模型和通过问卷和其他方式评估的暴露进行补充。这些数据将根据儿童的发育状况进行检查，即自闭症谱系障碍（ASD）、发育迟缓（DD）、特定言语/语言迟缓和其他轨迹，以及与免疫功能标记物的关联。项目 3 和项目 2 的表观遗传标记。将根据相关遗传多态性、CNV 或全局 DNA 甲基化测量来评估 PBDE、PFC 和拟除虫菊酯的差异影响，并考虑与这些化合物相关的机制途径。宾夕法尼亚州立大学的生物信息学团队，我们将以发现为导向的模式，探索生物标本、访谈和医疗记录中的各种暴露，以及遗传信息和表观遗传数据。