GEARs Combining advances in Genomics and Environmental science to accelerate Actionable Research and practice in ASD

ABSTRACT: This application seeks to establish a network for the investigation of gene-environment interaction in autism spectrum disorder (ASD) and outcomes among people with ASD. Much like the Psychiatric Genetics Consortium launched a unifying infrastructure for scaling genome-wide association studies in ASD, the Combining advances in Genomics and Environmental science to accelerate Actionable Research and practice in ASD (GEARs) Network effort will allow a centralized mechanism for GxE activities in ASD across multiple studies. Robust evaluation of GxE requires a large sample size, harmonized data on both genetics and the environment, and novel statistical methods for measuring and summarizing environments, genetics, and phenotypes. The GEARs Network seeks to compliment work in population studies with experimental models leveraging 3D brain organoids, reflecting multiple ASD-associated genetics backgrounds on which the impact of environmental risk can be evaluated on ASD-relevant neurophysiology endpoints. Finally, the GEARs Network will develop and implement a pipeline for outreach and dissemination of GxE findings. The successes of ASD genomics, emerging environmental evidence, and models of effective network collaborations for large-scale efforts make this the ideal time to create a GxE infrastructure for ASD research. Our team is uniquely poised to lead the GEARs Network, creating this opportunity at scale for the first time, and with a focus on both etiology and health outcomes among people with ASD. We have experience in leading multi-site collaborations, expertise in population and laboratory science, and required partnerships to foster communication across researchers and with the broader ASD community. This translational approach, informed by public health, will lead to improved understanding of both causes and consequences of ASD.