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: 10705830
• 负责人: JONATHAN S BERG
• 金额: $ 91.8万
• 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/10705830
• 关键词: Address; Adult; Age; Age of Onset; Applied Genetics; 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; Infant; Inherited; Intervention; Interview; Laboratories; Leadership; Longevity; Longitudinal Studies; Maps; Measures; Methods; Modeling; Neonatal Screening; Newborn Infant; Outcome; Parents; Pediatrics; Perception; Physicians; Pilot Projects; Population; Primary Care; Process; Protocols documentation; Provider; Public Health; Qualitative Methods; Research; Resources; Risk; Screening Result; Site; Specific qualifier value; Symptoms; Technology; Time; Training; Training and Education; Treatment Efficacy; Underrepresented Populations; Underserved Population; Variant; Visit; Well Child Visits; Work; age group; clinical trial implementation; clinically actionable; clinically relevant; community based participatory research; community clinic; community engagement; 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; pragmatic study; prevent; primary care setting; programs; rare mendelian disorder; 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.

项目摘要/摘要 基因组测序提供了识别临床相关遗传变异的前所未有的机会，但 在可以定期应用这项技术之前，需要克服许多挑战 人口及时识别患有可行疾病的人，以预防或改善症状。这 项目探讨了创新的基于年龄的基因组筛查（ABG）范式，旨在提供目标 以及通过孩子的日常健康访问给父母的高度可行的遗传信息，从而避免 基因组规模测序的一些更困难的方面，同时保留大多数好处。我们将 利用一个既定的度量标准，该指标评估与“临床可行性”相关的参数 发作和/或干预年龄，以确定适用于筛查的条件。在 与潜水员专家审议小组的合作，我们将定义一个共识框架 在婴儿期和童年期间，在指定的时间点使用有针对性的测序面板的ABG计划。 我们将吸引社区利益相关者提高对ABG计划的认识并获得关键反馈 告知可访问的学习材料的开发。我们将应用遗传医学实施 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者 并制定解决方案的策略。最后，我们将在少数小学 评估初步结果的护理儿科诊所，包括父母和提供者的观点，以及 ABG的可行性，可接受性和效用。该提案的预期结果是经过验证的， 利益相关者信息和实用的ABG计划，其中包括数百条可行的条件 在整个生命周期中，为未来的纵向研究奠定了基础 评估临床和健康经济成果。通过这项工作，我们将采用以社区为基础的 参与研究方法，以寻求潜水利益相关者的观点并强调 在各种环境中研究ABG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，该计划远远超出了新生儿筛查，可以 将其纳入常规井子保健中。我们设想该程序还将为个人做好准备 关于成人发病的潜在益处和筛查风险的明智明智的决定 成年期的条件，因此在所有年龄段的基因组筛查工作之间建立了联系。

项目成果

Parental Guidance Suggested: Engaging Parents as Partners in Research Studies of Genomic Screening for a Pediatric Population.

• DOI: 10.3389/fgene.2022.867030
• 发表时间: 2022
• 期刊: Frontiers in genetics
• 影响因子: 3.7
• 作者: Powell SN;Byfield G;Bennetone A;Frantz AM;Harrison LK;James-Crook ER;Osborne H;Owens TH;Shaw JL;O'Daniel J;Milko LV
• 通讯作者: Milko LV

Age-Based Genomic Screening during Childhood: Ethical and Practical Considerations in Public Health Genomics Implementation.

• DOI: 10.3390/ijns9030036
• 发表时间: 2023-06-27
• 期刊: International journal of neonatal screening
• 影响因子: 3.5