Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism

项目总结

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.