Harnessing Clinical Genomic Characterization to Accelerate Translational Advances for Patients with IDD

利用临床基因组特征加速 IDD 患者的转化进展

基本信息

批准号：
10159337
负责人：
JOHN N. CONSTANTINO
金额：
$ 125.21万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-06 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10159337
关键词：
Address Affect Award Biological Markers Biology Brain Brain Diseases Brain imaging Clinical Clinical Data Clinical Treatment Clinical Trials Clinical and Translational Science Awards Data Data Commons Disability phenotype Disease Electroencephalography Electronic Health Record Eligibility Determination Ensure Etiology Genes Genetic Genetic Diseases Genetic Predisposition to Disease Genetic Variation Genomics Genotype Health Health system Individual Infrastructure Institutes Institution Insurance Carriers Intellectual and Developmental Disabilities Research Centers Intellectual functioning disability Intervention Investigation Joints Laboratories Lead Link Medical Genetics Methods Molecular Abnormality National Institute of Child Health and Human Development Nature North Carolina Outcome Pathogenesis Pathogenicity Pathway interactions Patients Pharmacology Phenotype Population Attributable Risks Process Protocols documentation Registries Research Resources Risk Role Science Scientist Specific qualifier value Standardization Technology Testing Translational Research United States National Institutes of Health Universities Validation Variant Washington base design effective therapy experience genetic disorder diagnosis genetic variant genomic data improved individual patient innovation loss of function neurobehavioral novel open data patient oriented patient population patient registry personalized approach personalized intervention personalized medicine phenotypic data programs resilience response symptomatology treatment response

项目摘要

Abstract The last decade of clinical progress in intellectual and developmental disabilities (IDD)—which affect one in six individuals in the U.S.—has been characterized by unprecedented advances in understanding the nature and complexity of genetic susceptibility to IDD. Rare copy number and sequence variants are now known to account for a major share of population-attributable risk for IDD, and are being identified in over 30% of individuals who undergo clinical genomic sequencing. Clinical identification of pathogenic variants has generated major translational opportunities to accelerate discovery and improve clinical treatment, but these opportunities are constrained by serious gaps in our understanding of how to estimate the pathogenicity of a given genetic abnormality in an individual patient. This U01 Collaborative Innovation Award of the Clinical and Translational Science Award (CTSA) Program addresses this major roadblock, capitalizing upon the fact that genomic information is now commonly acquired in clinical settings and substantially subsidized by U.S. health insurers. Ensuring that clinically-acquired sequencing data of IDD patients is systematically integrated with standardized information on neurobehavioral variation and clinical course (this is currently uncommon) stands to accelerate understanding of the relationship between genetic variation and disease. The aims of this program are to establish standards for feasible neurobehavioral characterization of IDD patients in clinical health systems across the CTSA Network, to integrate phenotypic and clinical genomic characterization of patients to directly promote progress in the national agenda for IDD gene and variant curation, and to establish a dynamic, state-of-the-art IDD patient registry, as an extension of NCAT’s Center for Data To Health (CD2H) Initiative. This registry will be designed to co-register phenotypic, genotypic, and electronic health record data on brain imaging, EEG, laboratory biomarkers, and clinical course, for the purpose of specifying nuanced profiles of risk, resilience, and intervention response, and to elucidate both common and rare pathogenic mechanisms in IDD. Once established, the CTSA-IDD Registry will constitute a self-perpetuating open science platform for translational advances in IDD, by providing major new opportunity for patients affected by individually-rare IDD conditions to be identified by qualified scientists and clinicians, to be sub grouped according to genetic or phenotypic profile, and to participate in focused discovery efforts, clinical trials, and/or innovations in personalized intervention specific to their conditions.

抽象的智力和发展性不像临床计划的最后十年（IDD）影响美国的一个人 - 已经以前所未有的进步为特征了解对IDDD的遗传敏感性的自然和复杂性。众所周知，序列变体可以占人群征收风险的主要份额 IDD，在超过30％的临床基因组序列的个体中被鉴定出来。病原体变体的临床鉴定已经为加速发现并改善临床治疗，但机会受到限制我们理解的严重差距估计给定遗传的致病性单个患者的异常。转化科学奖（CTSA）计划涉及这一主要障碍，资本化基因组信息现在通常是在临床环境中获得的，并且大量获得由美国卫生保险公司补贴。患者系统地与有关神经行为变化的标准化信息整合和临床课程（目前很少），可以加速对遗传变异与疾病之间的关系。 IDD患者在临床卫生系统中可行的神经黑维表征的标准整个CTSA网络，整合表型和临床基因组表征患者直接促进IDD基因变体Curiant Curiant Curiant Curration的国家议程的进展并建立动态的，最先进的IDDDDDDD患者注册表，作为NCAT中心的扩展对于健康（CD2H）的数据，该注册表将被设计为共同注册的表型基因型和电子健康记录有关脑成像，脑电图，实验室生物标志物以及以及临床课程，目的是指定风险，弹性和干预的细微差别响应，并阐明IDD中的常见和罕见的致病机制。 CTSA-Advertry已建立，将征服一个自我延续的开放科学平台形式 IDD的翻译进展，为受影响的患者提供主要的新机会合格的科学家和临床医生将确定的个人稀有IDD遏制根据遗传或表型概况进行分组，并参与重点的发现工作，临床试验和/或针对其条件的个性化干预规范的创新。