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.

项目概要 哥伦比亚自闭症中心的前瞻性遗传风险评估（PROGRESS） 大学将加速基于不同人群的新生儿队列的多学科研究，重点关注 生命早期识别自闭症基因组风险变异，父母接受该基因的经验 信息以及早期神经行为轨迹分析以预测自闭症。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基因诊断的平台 - 提供了早期干预的机会，但也提出了许多有关家庭影响和 对孩子进行适当的管理。尽管早期干预可以改善自闭症的结局，但目前 尚无确定的神经行为标记来预测遗传风险婴儿的自闭症。以其统一的主题 推进自闭症遗传风险的早期评估：基础、影响和潜力 PROGRESS 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来解决自闭症研究中的这些差距。我们将利用资金 在纽约的 100,000 名不同人群的婴儿中试点全基因组测序的项目 City，使我们能够识别与自闭症高风险相关的罕见、单基因（例如 CHD8）病症 前瞻性地招募并纵向跟踪 240 名已确定患有自闭症遗传风险 (IGR) 的婴儿（约 400 名婴儿） 符合条件）和由 120 名没有确定的自闭症遗传风险（非 IGR）婴儿组成的匹配组（一起 包括 PROGRESS 队列）。因为经历和态度可能因种族、民族和文化的不同而不同 社会经济地位，我们多样化的、基于人群的队列将最大限度地提高我们的研究结果的普遍性。这 围绕这一群体建立了三个拟议的中心研究项目。项目1将鉴定基因和遗传 通过使用现有的大型基因组数据集和前瞻性评估来改进自闭症风险预测的变体 PROGRESS 队列中的基因组风险预测。项目 2 将审查近期和长期影响 PROGRESS 父母接受有关心理社会功能和父母自我效能的遗传信息的情况 队列婴儿。项目 3 将识别新出现的神经行为轨迹并评估这些轨迹的效用 改善 IGR 婴儿后期自闭症诊断预测的轨迹。这些相互关联的项目 将得到四个核心的支持，这也将成为当地、国家和全球自闭症患者的卓越资源 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；以及新自闭症研究人员的能力建设。