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

GEARs 结合基因组学和环境科学的进步，加速 ASD 的可操作研究和实践

基本信息

批准号：
10698145
负责人：
Christine Ladd-Acosta
金额：
$ 228.44万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-06 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10698145
关键词：
16p11.2 3-Dimensional Acceleration Address Air Pollution Biological Biological Models Brain Cell Line Characteristics Collaborations Communication Communities Data Collection Development Diagnosis Disease Environment Environmental Impact Environmental Risk Factor Environmental Science Etiology Evaluation Experimental Models Family Folic Acid Fostering Future Gene Mutation Genetic Genetic Risk Genomic approach Genomics Health Heavy Metals Heritability In Vitro Individual Infection Inflammation Infrastructure Investigation Laboratories Manuscripts Measures Mental Health Modeling National Human Genome Research Institute Network Infrastructure Neurodevelopmental Disorder Obesity Organoids Outcome Pathway Analysis Persons Phenotype Population Population Study Process Public Health Publishing Research Research Personnel Resources Risk Sample Size Science Severities Shapes Site Sleep Social Interaction Statistical Methods Structure Testing Time Translating Translations Vitamins Work autism community autism spectrum disorder autistic cohort comorbidity data harmonization design disorder risk experience experimental study gastrointestinal symptom gene environment interaction genetic variant genome sciences genome wide association study genome-wide high risk improved in vitro testing individuals with autism spectrum disorder induced pluripotent stem cell neuroinflammation neurophysiology novel outreach phenotypic data physical conditioning prenatal psychogenetics rare variant repetitive behavior social communication success synaptogenesis trait translational approach transmission process

项目摘要

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.

抽象的：该应用程序旨在建立一个用于研究自闭症基因与环境相互作用的网络谱系障碍 (ASD) 和 ASD 患者的结果。很像精神遗传学联盟启动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步来加速可操作的研究和 ASD 实践 (GEAR) 网络工作将为 ASD 中的 GxE 活动建立一个集中机制多项研究。 GxE 的稳健评估需要大量样本、两种遗传学的统一数据和环境，以及用于测量和总结环境、遗传学、和表型。 GEARs 网络旨在通过实验来补充人口研究工作利用 3D 大脑类器官的模型，反映了多种与 ASD 相关的遗传学背景环境风险的影响可以通过 ASD 相关的神经生理学终点来评估。最后， GEARs Network 将开发并实施一个用于推广和传播 GxE 研究结果的渠道。这 ASD 基因组学的成功、新出现的环境证据和有效网络模型大规模合作使得现在成为为 ASD 研究创建 GxE 基础设施的理想时机。我们的团队拥有独特的优势，能够领导 GEARs 网络，首次大规模创造这一机会，重点关注自闭症谱系障碍患者的病因学和健康结果。我们有经验领先的多地点合作、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，公共卫生部门的信息将有助于加深对自闭症谱系障碍的原因和后果的了解。

项目成果

期刊论文数量（1）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Deconvoluting gene and environment interactions to develop an "epigenetic score meter" of disease.

DOI：
10.15252/emmm.202318208
发表时间：
2023-09-11
期刊：
EMBO MOLECULAR MEDICINE
影响因子：
11.1
作者：
Butera, Alessio;Smirnova, Lena;Ferrando-May, Elisa;Hartung, Thomas;Brunner, Thomas;Leist, Marcel;Amelio, Ivano
通讯作者：
Amelio, Ivano