Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism

项目总结 哥伦比亚大学自闭症中心的前瞻性遗传风险评估(进展) 大学将在以人口为基础的多样化新生儿队列中加速多学科研究，重点是 自闭症的基因组风险变异的早期生命鉴定，父母接受该基因的经验 信息，以及对早期神经行为轨迹的分析来预测自闭症。新生儿筛查使用 基因组测序是一个平台，可以在自闭症症状出现之前提供基因诊断- 为早期干预提供了机会，但也引发了许多关于家庭影响和 对孩子的适当管理。尽管早期干预改善了自闭症的结果，但目前有 没有确定的神经行为标记物来预测遗传高危婴儿的自闭症。其统一的主题是 推进自闭症遗传风险的早期评估：基础、意义和潜力 进步中心将利用基因组学、发育神经科学、自闭症诊断、 心理社会评估和数据科学，以解决自闭症研究中的这些差距。我们将利用资助的 在纽约10万名婴儿组成的不同人群中进行全基因组测序试点项目 城市，使我们能够识别罕见的单基因(例如，CHD8)与自闭症的高风险相关的疾病 前瞻性登记并纵向跟踪240名患有自闭症遗传风险(IGR)的婴儿(满分400分) 符合条件的)和匹配的120名没有自闭症遗传风险(非IGR)的婴儿(一起 包括进步队列)。因为经历和态度可能会因种族、民族和 社会经济地位，我们多样化的、以人口为基础的队列将最大限度地推广我们的研究结果。这个 三个拟议的中心研究项目就是围绕这一群体而建立的。项目1将确定基因和基因 通过使用现有的大基因组数据集改进自闭症风险预测的变体并进行前瞻性评估 进展队列中的基因组风险预测。项目2将审查直接和长期的影响 接受关于心理社会功能和父母自我效能感的遗传信息在进展中的父母 队列婴儿。项目3将确定新出现的神经行为轨迹，并评估这些轨迹的实用性 改善IGR婴儿日后自闭症诊断的轨迹。这些相互关联的项目 将由四个核心支持，这四个核心也将是地方、国家和全球自闭症的卓越资源 创新分析策略的研究人员；严格的诊断方法；支持和参与 研究中的自闭症社区；以及新的自闭症研究人员的能力建设。

PROJECT SUMMARY The Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism Center at Columbia University will accelerate multidisciplinary research in a diverse population-based newborn cohort focused on early life identification of genomic risk variants for autism, parent experience with receiving this genetic information, and the analysis of early neurobehavioral trajectories to predict autism. Newborn screening using genomic sequencing is a platform that can deliver genetic diagnoses before autism symptoms emerge – providing the opportunity for early intervention but also raising numerous questions about family impact and appropriate management of the child. Although early intervention improves autism outcomes, there currently are no established neurobehavioral markers to predict autism in genetically at-risk infants. With its unifying theme of Advancing Early Evaluation of Genetic Risk in Autism: Foundations, Implications, and Potential, the PROGRESS Center will harness expertise in genomics, developmental neuroscience, autism diagnosis, psychosocial assessment, and data science to address these gaps in autism research. We will leverage a funded project piloting whole genome sequencing in a diverse population-based group of 100,000 infants in New York City, allowing us to identify rare, monogenic (e.g., CHD8) conditions associated with high risk for autism to prospectively enroll and longitudinally follow 240 infants at identified genetic risk (IGR) of autism (out of ~400 eligible) and a matched group of 120 infants without identified genetic risk (non-IGR) of autism (together comprising the PROGRESS cohort). Because experiences and attitudes likely vary across race, ethnicity, and socioeconomic status, our diverse, population-based cohort will maximize generalizability of our findings. The three proposed Center Research Projects are built around this cohort. Project 1 will identify genes and genetic variants to improve autism risk prediction by using large existing genomic datasets and prospectively evaluate genomic risk prediction in the PROGRESS cohort. Project 2 will examine the immediate and longer-term impact of receiving genetic information on psychosocial function and parental self-efficacy in parents of PROGRESS cohort infants. Project 3 will identify emerging neurobehavioral trajectories and assess the utility of these trajectories in improving the prediction of later autism diagnosis among IGR infants. These inter-related Projects will be supported by four Cores that also will be a resource of excellence to local, national, and global autism researchers for innovative analytic strategies; rigorous diagnostic methods; support for and engagement of autism communities in research; and capacity building for new autism researchers.