This proposal seeks to establish a Virtual Consortium for Translational/Transdisciplinary Environmental Research (ViCTER) to build the investigative expertise to study the mechanism underlying established air pollution associations for Autism Spectrum Disorder (ASD) though complimentary mouse and epidemiologic studies. We build on the first prospective R01 (R01 ES023780) evaluating the relationship between prenatal air pollutant exposures, cognitive deficits, and ASDs. Our team and others have previously reported increased risk of ASD based on living near freeways, exposure to near roadway air pollution (NRAP), and to increasing levels of particulate matter less than 2.5 microns in diameter (PM2.5) during gestation. However, few studies have examined joint effects of the environment and genetics and support from in vivo models is limited. This ViCTER brings together investigators with the necessary expertise to study joint effects of genes and the environment in both mouse and human studies to address critical data gaps. In this proposal we leverage resources of the Early Autism Risk Longitudinal Investigation (EARLI) and the mouse exposure paradigm developed as part of the University of Southern California Children's Environmental Health Center (SC-CEHC) to integrate findings from animal and human data addressing susceptibility to prenatal air pollution exposure for ASD. The ViCTER seeks to accomplish this through the following three projects: (1) to investigate the effect of prenatal near-roadway nano-scale particles (nPM) exposure on mouse behavior and on transcription in mouse brain and mouse peripheral blood; (2) to explore if prenatal NRAP and PM2.5 exposure are associated with differential epigenetic and transcription profiles in cord blood from EARLI, and if these profiles are associated with ASD; and (3) to expand the investigation of prenatal NRAP and PM2.5 effects on ASD in EARLI to incorporate genetic susceptibility. Taken together, findings from this consortium have the potential to rapidly influence our knowledge of gene-environment interaction and provide a structure for future integrative studies that would not be possible without development of this collaborative framework.
This proposal creates a virtual consortium to study the underlying mechanism of gene-air pollution effects for autism spectrum disorder (ASD) and neurodevelopment. We build on an existing R01 evaluating the effect of prenatal air pollution exposure in a unique prospective study of infants at high risk for ASD and developmental delays, where prenatal air pollution exposure has been assigned and quantitative phenotype assessments have been collected. This consortium will integrate data on transcription from mouse exposure models and data on epigenetics and transcription in cord blood from the infants to evaluate the mechanism underlying observed epidemiologic relationships. Results from this work will identify new gene-environment interactions for ASD and provide insight into the biological mechanism of air pollution effects on ASD, supporting public health interventions for air pollution exposure.
