Clinical and Genetic Analysis of Retinopathy of Prematurity

早产儿视网膜病变的临床和遗传学分析

• 批准号: 8258001
• 负责人: MICHAEL F. CHIANG
• 金额: $ 73.28万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-30 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8258001
• 关键词: Address; Algorithms; Alleles; Biomedical Research; Birth Weight; Blindness; Blood Vessels; Candidate Disease Gene; Caucasians; Caucasoid Race; Childhood; Clinical; Clinical Data; Clinical Medicine; Cohort Studies; Computers; DNA; Data; Development; Disease; Disease susceptibility; Electronic Health Record; Environmental Exposure; Environmental Risk Factor; Ethnic Origin; Future; Genetic; Genetic Markers; Genetic Materials; Genetic Risk; Genomics; Genotype; Goals; Health; Healthcare; Image; Image Analysis; Imaging Device; Infant; Informatics; Information Management; Judgment; Knowledge; Longitudinal Studies; Measurement; Methods; Modeling; Molecular Genetics; Online Systems; Ophthalmology; Outcome; Oxygen; Pathogenesis; Pathway interactions; Phenotype; Predisposition; Premature Birth; Premature Infant; Premature Infant Diseases; Recording of previous events; Recruitment Activity; Research; Research Personnel; Research Project Grants; Retinal; Retinopathy of Prematurity; Risk; Risk Factors; Sampling; Single Nucleotide Polymorphism; System; Testing; United States; Visual; Work; angiogenesis; base; bioimaging; biomedical informatics; case control; cohort; data management; density; disorder risk; genetic analysis; genetic variant; high risk; improved; neovascular; neovascularization; prototype; public health relevance; trait

DESCRIPTION (provided by applicant): The long-term goal of this project is to identify clinical and genetic features of retinopathy of prematurity (ROP) development, and to analyze their relationships. Although biomedical research data are being generated at an enormous pace, much less work has been done to integrate disparate scientific findings across the spectrum from genomics to imaging to clinical medicine. Our overall hypotheses are that genetic factors are involved in the initiation and modulation of ROP pathogenesis, and that there are etiological relationships among clinical, imaging, and genetic findings in ROP. These hypotheses will be tested using two sequential Specific Aims: (1) Recruit, phenotype, and collect genetic material from a cohort of over 1460 premature infants at- risk for ROP from 7 study centers. Data will be stored in a web-based data management system that will be developed for this project. Demographic and clinical features from three serial ophthalmoscopic examinations will be ascertained fully, and serial wide- angle images will be captured. DNA will be isolated and prepared for genotyping. (2) Quantify retinal vascular features using computer-based image analysis, and analyze relationships between clinical and image findings in ROP. Models for integrating the effects of quantitative image traits, clinical features, and environmental risk factors on ROP susceptibility will be estimated. Genotyping, genetic analysis, recruitment of additional subjects as needed, and modeling of clinical and genetic traits will be pursued during competitive renewal of this project. Ultimately, these studies should improve understanding of neovascularization in ROP and related ocular diseases, and of normal vascular development in infants. In addition, this work should demonstrate a prototype for health information management which combines genotypic and phenotypic data. This project will be performed by a multi-disciplinary team of collaborative investigators with expertise in clinical ophthalmology, biomedical informatics, genetic analysis, and statistical genetics. PUBLIC HEALTH RELEVANCE: ROP is a leading cause of childhood blindness in the United States and throughout the world, and the number of infants at risk for disease is increasing as the rate of premature birth rises. Rapidly-progressive changes associated with retinal vascular development and angiogenesis may be visualized by clinical examination, captured by wide-angle imaging, and analyzed genetically. Findings from this project should improve our understanding of the pathogenesis of ROP and other neovascular diseases, and provide better methods for identifying infants who are at highest risk of developing disease.

描述（由申请人提供）：该项目的长期目标是确定视网膜早产（ROP）发育的临床和遗传特征，并分析其关系。尽管生物医学研究数据正在以巨大的速度产生，但是从基因组学到影像学到临床医学的整个频谱中不同的科学发现进行的工作要少得多。我们的总体假设是，遗传因素与ROP发病机理的起始和调节有关，并且在ROP中临床，成像和遗传发现之间存在病因关系。这些假设将使用两个顺序的特定目的进行检验：（1）招募，表型和从1460多名早产儿的同类中收集遗传物质，这可能是7个研究中心的ROP风险。数据将存储在基于Web的数据管理系统中，该系统将为该项目开发。将充分确定三个连续眼镜检查的人口和临床特征，并将捕获串行宽角度图像。 DNA将被分离并制备用于基因分型。 （2）使用基于计算机的图像分析来量化视网膜血管特征，并分析ROP中临床和图像发现之间的关系。将估计用于整合定量图像特征，临床特征和环境风险因素对ROP敏感性的影响的模型。在该项目的竞争性更新期间，将追求基因分型，遗传分析，根据需要募集其他受试者以及临床和遗传特征的建模。最终，这些研究应提高对ROP和相关眼疾病的新血管形成的理解，以及对婴儿正常血管发育的理解。此外，这项工作应展示结合基因型和表型数据的健康信息管理原型。该项目将由一个由合作研究人员组成的多学科团队，具有临床眼科，生物医学信息学，遗传分析和统计遗传学方面的专业知识。 公共卫生相关性：ROP是美国和全世界儿童失明的主要原因，随着早产率的上升，处于疾病风险的婴儿人数正在增加。与视网膜血管发育和血管生成相关的快速促进变化可以通过临床检查可视化，通过广角成像捕获，并通过遗传分析。该项目的发现应提高我们对ROP和其他新血管疾病的发病机理的理解，并为识别患有最高患病风险的婴儿提供更好的方法。