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

摘要 MARBLES（婴儿自闭症风险标记：学习早期迹象）研究于2006年启动， 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）儿童的弟弟妹妹，开始随访期间（和之前）， 产前阶段，ASD和其他神经发育结果可能起源。 基于人群的队列，由于ASD患病率相对较低，因此需要非常大的样本量 （目前为1/68）8，通常无法进行ASD的金标准诊断， 设计利用参与者在发展ASD和其他 神经发育的结果，实现巨大的效率。高风险年轻人的既往队列 出生后招募的兄弟姐妹没有解决非遗传性和潜在的可改变的病因因素。 早期登记提供了一个机会，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志物。 鉴于ASD的患病率日益增加，现在比以往任何时候都更重要的是投资于研究，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，目前还没有很好地理解。该项目涉及两个 通过维持和加强MARBLES富集风险队列的资源基础设施，缩小差距。 保留该队列并对风险因素、机制标志物和结局进行深入评价至关重要 评估和早期鉴定易感人群中ASD的新出现的病因因素， 就像煤矿里的金丝雀，用来识别影响神经发育的暴露。我们这群人 数据和样本将允许分析与明确定义的临床 神经发育结果，我们丰富的机械生物标志物的特征可以识别 涉及易感性的途径和特征。我们建议继续招募和随访参与者 美国仅有的一个高风险ASD队列，前瞻性收集了妊娠数据和生物样本 这是目前在无成本扩展（NCE）。此外，我们建议进一步发展和维持我们的 用于扩展数据和样本存储库的存储库基础设施， 分享和促进对新出现的环境暴露和分子机制的调查 与ASD和其他不良神经发育状况的风险和表现相关的标志物。最后， 我们计划验证和可靠性测试环境暴露问题和措施，以供将来使用 问题研究这些目标的完成将有助于我们大量收集的数据和生物样本的合作共享 促进对新出现的环境暴露和分子机制标志物的研究， 与ASD和其他不良神经发育状况的风险和表现的关系。

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.