BUILDS MARBLES: Biorepository Upkeep and Infrastructure for Longitudinal Data Sharing for MARBLES

摘要 大理石(婴儿自闭症风险的标记物：学习早期征兆)研究于2006年由 加州大学戴维斯分校心理研究所和儿童环境健康中心作为第一个流行病学队列 自闭症谱系障碍(ASD)儿童的年幼兄弟姐妹在调查期间(和之前)开始随访 自闭症和其他神经发育结果可能发生的产前阶段1-7与 以人群为基础的队列，鉴于ASD的患病率相对较低，需要非常大的样本量 (目前68人中有1人)8并且通常不能进行ASD的黄金标准诊断，这是丰富的风险 设计利用了患有ASD和其他疾病风险极高的参与者 神经发育结果，实现了极高的效率。之前的高风险年轻人队列 出生后招募的兄弟姐妹没有解决非遗传和潜在的可改变的致病因素。 及早登记提供了一个机会，以检查广泛的环境暴露及其 机制，同时允许彻底搜索早期生物标记物。 鉴于ASD的患病率不断上升，8，11现在比以往任何时候都更关键地投资于研究，以确定 新出现的环境因素导致这些神经发育障碍的风险增加 其病因学的潜在机制，目前尚不清楚。这个项目既解决了这两个问题 通过维护和加强大理石丰富风险队列的资源基础设施，缩小差距。 保留这一队列并对风险因素、机械性标记和结果进行深入评估将是至关重要的 为了评估和早期识别易感人群中新出现的ASD病因， 作为煤矿中的金丝雀，用于识别影响神经发育的暴露。我们的同龄人是 数据和样本将允许分析与明确定义的临床相关的暴露的新问题 神经发育结果，以及我们对机械性生物标记物的丰富描述可以确定 涉及易感性的途径和特征。我们建议继续招募和跟踪参与者 拥有预期收集的妊娠数据和生物样本的仅有的具有丰富风险的ASD美国队列之一 目前处于无成本延期(NCE)。此外，我们建议进一步发展和维护我们的 用于扩展数据和示例存储库的存储库基础架构，以扩展协作 分享和促进新出现的环境暴露和分子机制的研究 与ASD和其他不利神经发育状况的风险和表现有关的标记物。最后， 我们计划验证和可靠性测试环境暴露的问题和措施，以供将来使用 学习。完成这些目标将有助于协作共享我们收集的大量数据和生物样本 为了促进对新出现的环境暴露和分子机制标记的研究 与ASD的风险和表现以及其他不利的神经发育状况的关系。

Abstract The MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) Study was launched in 2006 by the UC Davis MIND Institute and Center for Children's Environmental Health as the first epidemiologic cohort of younger siblings of children with autism spectrum disorders (ASD) to begin follow-up during (and before) the prenatal period when ASD and other neurodevelopmental outcomes are likely to originate.1-7 In contrast to population-based cohorts, which require very large sample sizes given a relatively low prevalence of ASD (currently 1 in 68)8 and typically are not able to conduct gold standard diagnosis of ASD, the enriched risk design takes advantage of participants at exceptionally high risk for developing ASD and other neurodevelopmental outcomes, achieving tremendous efficiencies. Previous cohorts of high-risk younger siblings recruited postnatally have not addressed non-inherited and potentially modifiable etiologic factors.9 Early enrollment provides an opportunity to examine a broad array of environmental exposures and their mechanisms, while simultaneously allowing thorough search for early biologic markers.10 Given increasing prevalence of ASD,8,11 it is more critical now than ever to invest in studies identifying emerging environmental factors responsible for increasing risk of these neurodevelopmental disorders and the mechanisms underlying their etiology, which are currently not well-understood. This project addresses both gaps by maintaining and enhancing the resource infrastructure of the MARBLES enriched-risk cohort. Retention of this cohort with deep evaluation of risk factors, mechanistic markers, and outcomes will be critical to evaluation and early identification of newly emerging etiologic factors for ASD in a susceptible population, serving as a canary in a coal-mine for identifying exposures that influence neurodevelopment. Our cohort's data and specimens will permit analyses of new questions on exposures in relation to well-defined clinical neurodevelopmental outcomes, and our rich characterization of mechanistic biomarkers could identify pathways and signatures of susceptibility involved. We propose to continue to enroll and follow-up participants of one of the only enriched-risk ASD U.S. cohorts with prospectively collected pregnancy data and biosamples that is currently in no cost extension (NCE). In addition, we propose to further develop and maintain our repository infrastructure for the expansive data and sample repositories in order to expand collaborative sharing and facilitate investigation of newly-emerging environmental exposures and molecular mechanistic markers in relation to risk and presentation of ASD and other adverse neurodevelopmental conditions. Finally, we plan to validate and reliability test environmental exposure questions and measures for use in future studies. Completion of these aims will assist collaborative sharing of our vast collection of data and biosamples to facilitate investigation of newly-emerging environmental exposures and molecular mechanistic markers in relation to risk and presentation of ASD and other adverse neurodevelopmental conditions.