Pediatric Autoimmune Consortium for Exposome Research (PACER)

项目摘要 虽然自身免疫性疾病（AID）发生在整个生命周期中，但许多AID的最早迹象可以首先在 儿童和青少年。早期发病的疾病可能与更积极的过程和风险， 并发症会随着时间的推移而积累。尽管疾病实体在受影响的组织方面存在差异， 危险因素的发生，这是惊人的注意到重要的共同主题的致病因素，从重叠， 风险基因与潜在环境触发因素的关系。自身免疫性疾病发病率的整体上升表明， 影响风险的持续环境变化。了解可变暴露对疾病的影响 发病机制有可能为有针对性的干预措施提供信息，这些干预措施可能会减缓或预防疾病的发展， 这些疾病在儿童和成年后的发展。 我们建议建立一个新的、第一个跨学科的研究团队， 基础设施需要为未来的大规模研究的作用，儿童艾滋病的麻烦。我们 总体目标是：1）建立合作伙伴关系，以利用现有的群体和资源; 2） 制定一个多领域、多层次的方法，全面审查艾滋病问题专家组的作用 途径;和3）开发新的战略，整合环境因素和遗传数据，使用切割- 边缘数据科学方法来调查儿童艾滋病的发展和进展。我们的具体 目标是： 目标1：建立一个多学科研究小组，并发展合作伙伴关系，以研究 通过（1A）在现有的研究中建立一个跨学科的联盟， 儿童援助）;（1B）对相关现有资源进行景观分析;以及（1C）组织两次 为期多天的研讨会，以发展和扩大现有的研究和合作。 目标2：探索战略，以解决全面衡量所需的多领域、多层次方法 通过（2A）评估其对患有AID儿童疾病途径的影响的麻烦和评估结构 对现有的测量和分析早期生命问题的方法进行全面分析， (2B)开发和扩展数据科学方法，用于整合多种数据类型，以确定精确的风险状况， 和（2C）通过在现有数据中生成试点分析来证明这些方法的效用。 目标3：开发和实施研究基础设施，以支持未来的EXACT工作。 影响：拟议的研究活动将为未来大规模的国家， 跨学科的合作研究网络，专注于在童年进行突破性的研究 援助

Project Summary While autoimmune disease (AID) occurs across the lifespan, the earliest signs of many AID can first be seen in children and adolescents. Early onset of disease can be associated with more aggressive course and the risk of complications accumulate over time. Despite diversity amongst disease entities in terms of tissues affected and risk factors for occurrence, it is striking to note important common themes in pathogenic factors, from overlap in risk genes to potential environmental triggers. The overall rising incidence of autoimmune diseases suggests ongoing enviromenal changes which impact risk. Understanding the impact of modifiable exposures on disease pathogenesis has the potential to inform targeted interventions that could slow or prevent the development and progression of these diseases in children and later adulthood. We propose to develop a new, first-of-its-kind transdisplinary research team to developing the infrasturcure needed to for a future large scale study on the role of the exposome in childhood AID. Our overarching goals are to: 1) establish collaborative partnerships to leverage existing cohorts and resources; 2) develop a multidomain, multilevel approach to comprehensively examine the role of the exposome on AID pathways; and 3) develop novel strategies for integrating environmental factors and genetic data using cutting- edge data science methodologies to investigate the development and progression of childhood AID. Our specific aims are: Aim 1: To establish a multidisciplinary research team and develop collaborative partnerships for studying the exposome in childhood AID by (1A) developing a transdisciplinary consortium across existing studies of childhood AID); (1B) conducting a landscape analysis of relevant existing resources; and (1C) organizing two multiday workshops to develop and expand existing research and collaborations. Aim 2: Explore strategies to address the multidomain, multilevel approach needed to comprehensively measure the exposome and assess constructs to evaluate their effect on disease pathways in children with AID by (2A) conducting a comprehensive analysis of existing methods for measuring and analyzing the early-life exposome (2B) develop and expand data science methods for integrating multiple data types to identify precise risk profiles, and (2C) demonstrate the utility of these approaches by generating pilot analysis in existing data. Aim 3: Develop and implement research infrastructure to support the future EXACT effort. IMPACT: The proposed research activities will lay the foundations for future large scale national, interdisciplinary, collaborative research network focused on performing groundbreaking research in childhood AID.