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

• 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
• 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

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.

摘要： 这个应用程序试图建立一个网络的调查基因-环境相互作用的自闭症 谱系障碍（ASD）和ASD患者的结局。就像精神遗传学 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步，加速可操作的研究， ASD（GEAR）网络工作的实践将允许ASD中的GxE活动的集中机制， 多项研究。GxE的稳健评价需要大样本量、两种遗传学的协调数据 以及测量和总结环境，遗传学， 和表型。GEARs网络力求通过实验性的人口研究工作， 利用3D脑类器官的模型，反映了多种ASD相关的遗传学背景， 环境风险的影响可以在ASD相关神经生理学终点上进行评估。最后 GEAR网络将开发和实施一个管道，用于推广和传播GxE调查结果。的 ASD基因组学的成功，新兴的环境证据和有效网络的模型 大规模的合作使这成为为ASD研究创建GxE基础设施的理想时机。 我们的团队是独一无二的准备领导GEARs网络，创造这个机会的规模首次， 并重点关注ASD患者的病因和健康结果。已有成熟经验的 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， 促进研究人员之间的沟通，并与更广泛的ASD社区。这种翻译方法， 通过公共卫生信息，将导致对ASD的原因和后果的更好理解。

项目成果

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