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， 第一个自闭症谱系障碍（ASD）儿童的弟弟妹妹的流行病学队列开始跟踪- 在ASD可能起源的产前期间和产前期间。与基于人口的队列相比， 由于ASD的患病率相对较低（1/44），因此需要大样本量，并且通常不能 进行ASD的金标准诊断，丰富风险设计通过招募 患有ASD（>20%）和其他神经发育问题（15-20%）的高家族风险参与者。 其他出生后招募的高危年幼兄弟姐妹队列，除了EARLI研究， 更长的注册。早期登记提供了一个机会，检查广泛的环境暴露 早期的生物标志物。鉴于ASD的患病率不断增加，投资研究确定因素至关重要 负责增加风险和ASD病因的机制，这还没有得到很好的理解。 该项目通过维护和加强大理石的基础设施来解决这两个差距， 风险队列。MARBLES研究已经为533名儿童招募了超过522名孕妇，并收集了近28，000名 样本，关于暴露、病史、饮食、生活方式和家庭因素的综合数据， 甲基化，表达，免疫，营养和污染物标记，并进行了丰富的表征， 使用金标准临床评估的神经发育结果。MARBLES研究采用了 多管齐下的招聘方法，包括各种社区外展活动， 社会人口统计学上多样化的队列允许检查一个群体的分布和关联的差异， 多种环境因素，包括种族、民族、出生、父母教育和其他社会经济因素 指标MARBLES团队有着支持科学和劳动力多样性的历史， 继续扩大这些努力。我们建议继续采用精简的 协议，现在将适应讲西班牙语的家庭，并扩大我们的在线存在，以更广泛的 共享资源，为美国唯一一个前瞻性收集妊娠数据的高风险ASD队列提供资源。 数据和生物样本，并深入评估风险因素、介质和结果，以促进发现 ASD的病因因素和早期生物标志物。我们将进一步努力了解种族、民族和 ASD诊断中存在的社会人口学差异可能是由结构性种族主义驱动的， 从我们的参与者那里收集关于经历过的歧视的信息， 因素这些目标的完成将显著丰富MARBLES资源，加快合作共享， 使我们和未来的合作者能够更好地解决在高风险队列中ASD预测因子的问题， 同时更彻底地调整混杂因素，包括结构性种族主义造成的因素， 增加对经历过的歧视如何在这些家庭的照顾和福祉中发挥作用的理解。

Abstract The MARBLES (Markers of Autism Risk in Babies: Learning Early Signs) Study was launched in 2006 as the first epidemiologic cohort of younger siblings of children with autism spectrum disorders (ASD) to begin follow- up before and during the prenatal period when ASD is likely to originate. In contrast to population-based cohorts that require large sample sizes given a relatively low prevalence of ASD (1 in 44) and typically are not able to conduct gold standard diagnosis of ASD, the enriched-risk design offers greater efficiency by enrolling participants at high familial risk for developing ASD (>20%) and other neurodevelopmental concerns (15-20%). Other cohorts of high-risk younger siblings recruited postnatally, with the exception of the EARLI study that is no longer enrolling. Early enrollment provides an opportunity to examine a broad array of environmental exposures and early biomarkers. Given increasing prevalence of ASD, it is critical to invest in studies identifying factors responsible for increasing risk and the mechanisms underlying ASD etiology, which are not yet well-understood. This project addresses both gaps by maintaining and enhancing the infrastructure of the MARBLES enriched- risk cohort. The MARBLES study has enrolled over 522 pregnancies for 533 children and collected nearly 28,000 samples, comprehensive data on exposures, medical history, diet, lifestyle, and home factors, measured methylation, expression, immune, nutrient, and contaminant markers, and conducted rich characterization of neurodevelopmental outcomes using gold-standard clinical assessments. The MARBLES study employed a multi-pronged recruitment approach that includes a variety of community outreach activities that resulted in a sociodemographically diverse cohort allowing examination of differences in distributions and associations of a multitude of environmental factors across race, ethnicity, nativity, parental education, and other socioeconomic indicators. The MARBLES team has a history of supporting both scientific and workforce diversity and will continue to expand these efforts. We propose to continue to enroll and follow participants under a streamlined protocol that will now accommodate Spanish-speaking families, and expand our online presence to more widely share resources for one of the only enriched-risk ASD cohorts in the U.S. with prospectively collected pregnancy data and biosamples and deep evaluation of risk factors, mediators, and outcomes, to advance discovery of etiologic factors and early biomarkers for ASD. We will further work to understand the racial, ethnic, and sociodemographic disparities that exist in the diagnosis of ASD that are likely driven by structural racism14 by collecting information from our participants on experienced discrimination and by linking to neighborhood-level factors. Completion of these aims will markedly enrich MARBLES resources, expedite collaborative sharing, and allow us and future collaborators to better address questions on predictors of ASD in an enriched-risk cohort, while more thoroughly adjusting for confounding factors including those resulting from structural racism, and will add understanding of how experienced discrimination plays a role in these families’ care and well-being.