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）：本项目的长期目标是确定早产儿视网膜病变（ROP）发展的临床和遗传特征，并分析它们之间的关系。尽管生物医学研究数据正在以巨大的速度产生，但在整合从基因组学到成像到临床医学等各个领域的不同科学发现方面所做的工作却少得多。我们的总体假设是遗传因素参与了ROP发病机制的启动和调节，并且在ROP的临床、影像学和遗传发现之间存在病因学关系。这些假设将通过两个连续的特定目标进行验证：(1)招募、表型分析和收集来自7个研究中心的1460多名有ROP风险的早产儿的遗传物质。数据将存储在将为此项目开发的基于网络的数据管理系统中。从三个系列的眼科检查中充分确定人口统计学和临床特征，并捕获一系列广角图像。DNA将被分离并准备用于基因分型。(2)利用计算机图像分析量化视网膜血管特征，分析ROP的临床与图像表现之间的关系。将评估整合定量图像特征、临床特征和环境风险因素对ROP易感性的影响的模型。基因分型、遗传分析、根据需要招募额外的受试者，以及临床和遗传特征的建模将在本项目的竞争性更新期间进行。最终，这些研究应该提高对ROP和相关眼部疾病新生血管的认识，以及对婴儿正常血管发育的认识。此外，这项工作应该展示一个结合基因型和表型数据的健康信息管理原型。该项目将由临床眼科学、生物医学信息学、遗传分析和统计遗传学方面的多学科合作研究人员组成。