Uncovering the Impact of Air Pollution Sources on Autism Spectrum Disorder: A Metabolomic Approach to Identifying Critical Biological Pathways - PROJECT SUMMARY Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder with rising prevalence, currently affecting 2.8% of children in the United States, with vast disparities based on race/ethnicity, neighborhood socioeconomic status, and region. While genetic factors play a significant role in ASD, growing evidence suggests that environmental exposures, particularly air pollution (AP), contribute to ASD risk. Despite well- established links between AP and adverse health outcomes, the specific sources and components of AP, such as traffic, wildfires, heat, and greenspace contributing to ASD remain unclear, and the biological pathways linking these exposures to ASD are not fully understood. This project aims to address these critical gaps by integrating advanced metabolomics with novel methods for assessing multiple pollutant exposures. This K99/R00 award will provide Dr. O’Sharkey with the opportunity to enhance his expertise in environmental epidemiology and air pollution by incorporating additional training in metabolomics, neurodevelopmental epidemiology, and advanced analytical methods for multiple exposures and mixtures. This project will offer valuable insights into the biological pathways linking ASD and air pollution source exposure by leveraging a large metabolomics dataset, enabling a deeper understanding of the mechanisms underlying this complex relationship. Aim 1 will investigate the association between various AP sources, including traffic-related pollutants, wildfire smoke, and environmental factors like heat and greenspace, with ASD risk using advanced statistical methods to disentangle the combined, synergistic, and individual effects of these exposures. Aim 2 will examine how specific AP sources and components influence neonatal metabolomic profiles, using blood spots, and investigate the effects of related exposures like excess heat and green space access. Aim 3 will identify and characterize biological pathways linking AP exposure to ASD by comparing metabolomic profiles between ASD and non-ASD populations using neonatal blood spots. By integrating metabolomic data, the project aims to uncover specific biomarkers and disrupted metabolic pathways associated with AP exposure, providing novel insights into the mechanisms underlying ASD. Through the mentorship of Drs. Mike Jerrett and Beate Ritz, and the advisory committee of Dr. Rebecca Schmidt, Dr. Doug Walker, Dr. Zeyan Liew, and Dr. Kimberly Paul, Dr. O'Sharkey will accomplish these aims with the support of field experts, benefiting from dedicated one-on-one guidance, extensive collaboration, and regular lab meetings to foster ongoing progress and learning. Through targeted coursework, workshops, seminars, and the K99/R00 award's support for attending conferences, Dr. O’Sharkey will gain advanced skills in environmental and metabolomics epidemiology, ensuring a comprehensive and multidisciplinary training experience. The findings of this research could significantly inform public health policies aimed at reducing specific sources, components, or mixtures of AP exposure during pregnancy, contributing to environmental epidemiology by revealing previously unknown metabolic pathways affected by low-concentration pollutants.
