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.

Project Narrative Autoimmune disease, including thyroid disease, celiac disease and type 1 diabetes are increasing in children. This research will bring together researchers with expertise in environmental exposures and autoimmune disease. We will use “big data” approaches on data collected over the past three decades to understand how changes in our environment are causing autoimmune disease in children.