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

摘要： 本申请旨在建立一个自闭症基因-环境相互作用研究网络。 谱系障碍(ASD)与ASD患者的预后。很像精神遗传学 该联盟推出了一个统一的基础设施，用于扩展ASD的全基因组关联研究 结合基因组学和环境科学的进展加速可操作的研究和 ASD(Gears)网络工作中的实践将为ASD中的GxE活动提供一个跨 多项研究。对GxE的稳健评估需要大量的样本量、关于两种遗传学的协调一致的数据 和环境，以及测量和总结环境、遗传学、 和表型。Gears网络试图通过实验来补充人口研究方面的工作 利用3D脑器官的模型，反映了ASD相关的多个遗传学背景 可以评估环境风险对ASD相关神经生理学终点的影响。最后， Gears Network将制定和实施一条推广和传播GxE调查结果的渠道。这个 ASD基因组学、新兴环境证据和有效网络模型的成功 大规模工作的协作使现在成为为ASD研究创建GxE基础设施的理想时机。 我们的团队独一无二地准备领导Gears Network，首次大规模创造这一机会， 重点关注ASD患者的病因学和健康结果。我们在以下方面有经验 领导多地点合作，人口和实验室科学方面的专业知识，以及所需的合作伙伴关系 促进研究人员之间以及与更广泛的ASD社区的沟通。这种翻译方法， 向公众健康提供信息，将有助于更好地了解自闭症的原因和后果。

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.