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前瞻性遗传风险评估 大学将加快多学科研究在一个多样化的人口为基础的新生儿队列，重点是 自闭症的基因组风险变异的早期生命识别，接受这种基因的父母经历 信息，以及分析早期神经行为轨迹来预测自闭症。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进行基因诊断的平台， 提供了早期干预的机会，但也提出了许多关于家庭影响的问题， 对孩子进行适当的管理。虽然早期干预可以改善自闭症的结果，但目前 没有确定的神经行为标志物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、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， 社会心理评估和数据科学来解决自闭症研究中的这些差距。我们将利用一个资金充足的 在纽约的一个以10万名婴儿为基础的多样化人群中进行全基因组测序的试点项目 城市，使我们能够识别罕见的，单基因（例如，CHD 8）与自闭症高风险相关的疾病， 前瞻性招募并纵向随访了240名有自闭症遗传风险（IGR）的婴儿（共约400名 合格）和120名没有确定的自闭症遗传风险（非IGR）的婴儿（一起） 包括PROGRESS队列）。因为经历和态度可能因种族、民族和宗教而异， 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提高我们的研究结果的普遍性。的 三个拟议的中心研究项目是围绕这一群体建立的。项目1将确定基因和遗传 通过使用现有的大型基因组数据集来改善自闭症风险预测，并前瞻性地评估 PROGRESS队列中的基因组风险预测。项目2将审查直接和长期影响 接受PROGRESS父母的心理社会功能和父母自我效能的遗传信息 婴儿队列。项目3将确定新出现的神经行为轨迹，并评估这些轨迹的效用。 轨迹，以提高IGR婴儿中自闭症诊断的预测。这些相互关联的项目 将得到四个核心的支持，这些核心也将成为地方、国家和全球自闭症的卓越资源。 研究人员创新的分析战略;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。