Age-based genomic screening in newborns, infants, and children: a novel paradigm in public health genomics

新生儿、婴儿和儿童基于年龄的基因组筛查：公共卫生基因组学的新范例

• 批准号: 10518804
• 负责人: JONATHAN S BERG
• 金额: $ 93.3万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-14 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10518804
• 关键词: Address; Adult; Age; Age of Onset; Awareness; Benefits and Risks; Biological Assay; Birth; Child; Child Care; Childhood; Clinic; Clinical; Collaborations; Communities; Consensus; Data; Decision Making; Development; Disease; Eligibility Determination; Ethics; Expert Opinion; Feedback; Future; Genetic Diseases; Genetic Medicine; Genomic medicine; Genomics; Goals; Health; Healthcare; Individual; Inherited; Intervention; Interview; Laboratories; Leadership; Longevity; Longitudinal Studies; Measures; Mendelian disorder; Methods; Modeling; Neonatal Screening; Newborn Infant; Outcome; Parents; Pediatrics; Perception; Physicians; Pilot Projects; Population; Primary Health Care; Process; Protocols documentation; Provider; Public Health; Qualitative Methods; Research; Resources; Risk; Screening Result; Site; Specific qualifier value; Symptoms; Technology; Time; Training; Treatment Efficacy; Underrepresented Populations; Underserved Population; Variant; Visit; Well Child Visits; Work; age group; base; clinical trial implementation; clinically actionable; clinically relevant; community based participatory research; community clinic; design; economic outcome; education resources; genetic information; genetic variant; genome sequencing; genome-wide; health economics; implementation facilitators; implementation framework; implementation outcomes; implementation strategy; implementation trial; improved; infancy; innovation; novel; organizational readiness; prevent; primary care setting; programs; reduce symptoms; research and development; screening; screening program; social; targeted sequencing; technology validation; whole genome

Project Summary/Abstract Genomic sequencing offers an unprecedented opportunity to identify clinically relevant genetic variants, yet there are many challenges to overcome before this technology can be applied routinely in the healthy population to identify individuals with actionable disorders in time to prevent or ameliorate symptoms. This project explores an innovative age-based genomic screening (ABGS) paradigm that aims to provide targeted and highly actionable genetic information to parents via their child’s routine wellness visits, thereby avoiding some of the more difficult aspects of genome-scale sequencing while retaining most of the benefits. We will utilize an established metric that evaluates parameters relevant to “clinical actionability” and defines the age of onset and/or the age of intervention, to identify conditions that would be applicable for screening. In collaboration with a diverse Expert Deliberative Group, we will define a consensus framework for carrying out the ABGS program using targeted sequencing panels at specified time-points during infancy and childhood. We will engage community stakeholders to raise awareness of the ABGS program and obtain critical feedback to inform the development of accessible study materials. We will apply the Genetic Medicine Implementation Research framework and utilize rigorous methods and measures to identify potential barriers and facilitators and develop strategies to address them. Finally, we will conduct a pilot project in a small number of primary care pediatrics clinics assessing preliminary outcomes, including perspectives of parents and providers, and the feasibility, acceptability, and utility of ABGS. The expected result of this proposal is a validated, stakeholder-informed, and practical ABGS program that includes hundreds of conditions that are actionable throughout the lifespan, setting the stage for a future longitudinal study in a larger number of practices that can assess clinical and health economic outcomes. Throughout this work, we will employ a community-based participatory research approach to seek out perspectives from diverse stakeholders and emphasize the importance of studying ABGS in a wide range of settings. The long-term goal of this research program is to create a broadly applicable genomic screening program that extends well beyond newborn screening and can be incorporated into routine well child care. We envision that this program will also prepare individuals to eventually make informed decisions about the potential benefits and risks of screening for adult-onset conditions during adulthood, thus creating a connection between genomic screening efforts in all age groups.

项目概要/摘要 基因组测序为识别临床相关遗传变异提供了前所未有的机会，但 在这项技术能够常规应用于健康领域之前，还有许多挑战需要克服 及时识别患有可采取行动的疾病的个体，以预防或改善症状。这 项目探索了一种创新的基于年龄的基因组筛查（ABGS）范式，旨在提供有针对性的 通过孩子的例行健康检查向父母提供高度可操作的遗传信息，从而避免 基因组规模测序的一些更困难的方面，同时保留了大部分好处。我们将 利用既定的指标来评估与“临床可操作性”相关的参数并定义年龄 发病和/或干预年龄，以确定适用于筛查的条件。在 与多元化的专家审议小组合作，我们将制定一个共识框架来执行 ABGS 计划在婴儿期和儿童期的特定时间点使用靶向测序面板。 我们将让社区利益相关者参与进来，以提高对 ABGS 计划的认识并获得重要反馈 为无障碍学习材料的开发提供信息。我们将应用基因医学实施 研究框架并利用严格的方法和措施来识别潜在的障碍和促进因素 并制定解决这些问题的策略。最后，我们将在少数基层进行试点。 儿科护理诊所评估初步结果，包括家长和提供者的观点，以及 ABGS 的可行性、可接受性和实用性。该提案的预期结果是经过验证的， 利益相关者知情且实用的 ABGS 计划，其中包括数百个可操作的条件 在整个生命周期中，为未来在大量实践中进行纵向研究奠定基础 评估临床和健康经济成果。在整个工作中，我们将聘请基于社区的 参与式研究方法，寻求不同利益相关者的观点，并强调 在广泛的环境中研究 ABGS 的重要性。该研究计划的长期目标是 创建一个广泛适用的基因组筛查计划，其范围远远超出新生儿筛查范围，并且可以 纳入日常儿童保育。我们预计该计划还将帮助个人做好准备 最终就成人发病筛查的潜在益处和风险做出明智的决定 成年期的条件，从而在所有年龄段的基因组筛查工作之间建立联系。