Clinical and Genetic Analysis of Retinopathy of Prematurity

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生成，但在整合从基因组学到成像到临床医学的各种不同科学发现方面所做的工作要少得多。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ROP的临床、影像学和遗传学发现之间存在病因学关系。这些假设将使用两个连续的特定目的进行检验：（1）从来自7个研究中心的超过1460名有ROP风险的早产儿队列中招募、表型和收集遗传物质。数据将储存在为该项目开发的基于网络的数据管理系统中。人口统计学和临床特征，从三个系列检眼镜检查将被充分确定，并连续广角图像将被捕获。将分离DNA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、临床特征和环境危险因素对ROP易感性的影响的模型。在本项目的竞争性更新期间，将继续进行基因分型、遗传分析、根据需要招募其他受试者以及临床和遗传特征建模。最终，这些研究将提高对ROP和相关眼部疾病中新生血管形成的理解，以及对婴儿正常血管发育的理解。此外，这项工作应展示一个原型的健康信息管理相结合的基因型和表型数据。该项目将由一个多学科的合作研究团队进行，该团队具有临床眼科学，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，并且随着早产率的上升，处于疾病风险中的婴儿数量正在增加。与视网膜血管发育和血管生成相关的快速进展性变化可以通过临床检查可视化，通过广角成像捕获，并进行遗传分析。该项目的发现将提高我们对ROP和其他新生血管疾病发病机制的理解，并提供更好的方法来识别处于最高疾病风险的婴儿。

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.