Expanding the Value of the EARLI study: Small Cohort with Big Data

包括自闭症在内的神经发育障碍(NDDS)影响着超过15%的美国儿童- 仅自闭症谱系障碍(ASD)就影响了大约1.5%的美国儿童。鉴定 可能导致初级和二级预防工作的根本原因。确凿的证据 支持基因和环境的共同作用，特别是产前暴露。 前瞻性研究，包括在怀孕期间、症状出现之前收集的暴露信息 虽然在普通人群中进行前瞻性研究是不可行的， 性价比高，或对ASD有效。丰富的家庭风险设计，它利用 ASD儿童的兄弟姐妹中ASD和NDD的实质性复发风险一直是 用于实现具有合理结果事件的前瞻性数据收集。最早的 自闭症风险纵向调查(EARLI)研究帮助引领了这种丰富的风险 队列方法。EARLI招募并跟踪了260多名已经有过 患有自闭症的儿童进行多次研究访问、儿童评估、生物采样和家庭环境 关于怀孕和出生前3年的调查。而总样本量受到限制； EARLI的值是纵向数据和分子测量的深度 组织类型和早期发育窗口期。迄今为止，已有超过94亿个数据点 在多种表型、组织、暴露和基因组测量中产生。海流 提案旨在保持和丰富这项有价值的研究，以充分认识到其对 环境健康。目标是：1.维护和扩展EARLI生物样本库 通过支持储存和回收工作以及增加和储存大棚乳牙 这将使对越来越多的毒物采取纵向产前暴露措施成为可能 曝光。2.测量学龄儿童同时出现疾病的频率和模式 为了更好地描述共出现的NDD和数量性状的表型。3. 描述重金属测量在时间、家庭成员和 母体的血液和尿液，以及脱落的乳牙。4.开发和应用方法 对于表型和使用潜在结构的暴露协调，允许内部和交叉 队列调查；5.迁移、增强和增加EARLI研究的重现性 数据以实现数据共享。EARLI的研究对早期生命环境是一项宝贵的资产 神经发育结果的流行病学。实现这些目标将使我们能够最大限度地 这项新的研究对理解ASD和NDD的病因学做出了贡献。

Neurodevelopmental disorders (NDDs), including ASD, affect over 15 percent of US children – Autism Spectrum Disorder (ASD) alone affects approximately 1.5% of US children. Identification of underlying causes can lead to primary and secondary prevention efforts. Substantial evidence supports contribution of both genes and environment, particularly prenatal exposures. Prospective studies, with exposure information collected during pregnancy, prior to symptom onset, are sorely needed although prospective studies in the general population are not feasible, cost effective, or efficient for ASD. The enriched-familial-risk design, which capitalizes on the substantial recurrence risk of both ASD and NDD among siblings of children with ASD, has been employed to achieve prospective data collection with reasonable outcome events. The Early Autism Risk Longitudinal Investigation (EARLI) study has helped to trailblaze this enriched risk cohort approach. EARLI recruited and followed over 260 pregnant women who already had a child with ASD with multiple study visits, child assessments, biosampling, and home environment surveys over pregnancy and the first 3 years of life. While the total sample size was constrained; the value of EARLI is the depth of longitudinal data and molecular measurements across multiple tissue types and early developmental windows. To date, over 9.4 billion data points have been generated across multiple phenotypes, tissues, exposures, and -omic measures. The current proposal seeks to maintain and enrich this valuable study to fully realize its impact on environmental health. The goals are to: 1. Maintain and extend the EARLI Biosample Repository through support of the storage and retrieval efforts and addition and storage of shed baby teeth that will enable longitudinal prenatal exposure measures across a growing array of toxicant exposures. 2. Measure frequency and patterns of emerging co-occurring conditions at school age to better characterize phenotypes across co-occurring NDDs and quantitative traits. 3. Characterize variability of heavy metals measurement across timing, family members, and matrices including maternal blood and urine and shed baby teeth. 4. Develop and apply methods for phenotype and for exposure harmonization using latent constructs, enabling within and cross- cohort investigations; 5. Migrate, enhance, and increase the reproducibility of EARLI research data to enable data sharing. The EARLI study is a valuable asset to early life environmental epidemiology of neurodevelopmental outcomes. Conducting these aims will allow us to maximize the contribution of this novel study to the understanding of ASD and NDD etiology.