Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism

自闭症的前瞻性遗传风险评估（PROGRESS）

• 批准号: 10531728
• 负责人: Wendy K Chung
• 金额: $ 238.48万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 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/10531728
• 关键词: 16p11.2; Address; Affect; Attitude; Autism Diagnosis; Behavioral; Brain; Caregivers; Child; Child Rearing; Clinical; Cognitive; Communication; Communities; Computer Analysis; Copy Number Polymorphism; Data Science; Data Set; Development; Diagnosis; Diagnostic Procedure; Doctor of Philosophy; Early Intervention; Enrollment; Ensure; Ethnic Origin; Evaluation; Family; Foundations; Funding; Genetic Risk; Genetic Screening; Genomics; Infant; Inherited; Interdisciplinary Study; Life; Matched Group; Measurement; Monitor; Neonatal Screening; Neurosciences; New York City; Newborn Infant; Outcome; Parents; Pathogenicity; Pilot Projects; Policies; Population Heterogeneity; Psychosocial Assessment and Care; Race; Research; Research Personnel; Research Project Grants; Resources; Risk; Self Efficacy; Sensory; Services; Socioeconomic Status; Standardization; Statistical Data Interpretation; Statistical Models; Symptoms; Syndrome; Systems Biology; Testing; Universities; Variant; Work; autism community; autism spectrum disorder; autistic children; base; cohort; congenital anomaly; exome sequencing; experience; genetic disorder diagnosis; genetic information; genetic variant; genome sequencing; genomic data; high risk; improved; infancy; innovation; neonate; neurobehavioral; outreach; population based; prospective; psychosocial; relating to nervous system; risk prediction; risk variant; social communication; trait; whole genome

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.

项目摘要 哥伦比亚自闭症中心的前瞻性遗传风险评估和评估（进度） 大学将加速以潜水员人群的新生同类群体的跨学科研究 自闭症基因组风险变异的早期生活鉴定，父母接受这种遗传的经验 信息，以及早期神经行为轨迹的分析以预测自闭症。新生儿筛查使用 基因组测序是一个可以在自闭症症状出现之前提供遗传诊断的平台 - 提供了早期干预的机会，同时也提出了有关家庭影响和 尽管早期干预改善了自闭症的结果，但目前有 没有建立的神经行为标记来预测一般风险婴儿的自闭症。以其统一的主题 提高自闭症遗传风险的早期评估：基础，影响和潜力， 进步中心将利用基因组学，发育神经科学，自闭症诊断的专业知识， 社会心理评估和数据科学，以解决自闭症研究中的这些差距。我们将利用资助的 在纽约的一个100,000名婴儿的潜水员人群中试用整个基因组测序的项目 城市，允许我们确定与自闭症高风险相关的稀有，单基因（例如CHD8）条件 在240名婴儿身后，前瞻性地入学和纵向，自闭症的遗传风险（IGR） 符合条件）和一个匹配的120名婴儿，没有发现自闭症的遗传风险（非元）（一起） 符合进度队列）。因为经历和参加的经验可能会在种族，种族和 社会经济地位，我们的潜水员，基于人群的队列将最大程度地提高我们发现的普遍性。 围绕该队列建立了三个提议的中心研究项目。项目1将识别基因和通用 通过使用大型现有基因组数据集来改善自闭症风险预测的变体并前瞻性评估 进度队列中的基因组风险预测。项目2将检查直接和长期影响 收到有关社会心理功能的遗传信息和进步父母的父母自我有效 队列婴儿。项目3将确定新兴的神经行为轨迹和评估这些效用 改善IGR婴儿后来自闭症诊断的预测的轨迹。这些相互关联的项目 将得到四个核心的支持，这也将是对地方，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。