Primary Open Angle African-American Glaucoma Genetics Study Renewal

摘要报表 原发性开角型青光眼(POAG)是一个紧迫的公共卫生问题 非裔美国人。这种疾病是导致这些地区不可逆转失明的主要原因。 个人。POAG对更年轻的非裔美国人的影响更严重，对 致视力丧失、健康和经济后果不良的年轻一代。 目前对这种疾病的降压治疗效果参差不齐， 大约30%的患者仍在经历视力丧失。开角型青光眼是家族性疾病 而且有必要进行大规模的基因研究来阐明疾病的机制。这 需求在非裔美国人中尤其明显，尽管他们的 对疾病负担的研究仍然严重不足。在最初的筹资阶段， 原发开角型非裔美国人青光眼遗传学研究 通过对非裔美国人进行有史以来最大规模的POAG遗传学研究，这种差异 从一个城市招募。为了这次更新，我们将研究来自基因组的基因数据- 7765名受试者的广谱关联研究和8082名受试者的全外显子组测序， 以及90%的POAG病例的丰富表型数据。拟议的续期将 使我们能够进一步调查和确定对非洲具有重要生物学意义的变异 美国普瓦格。这项研究的目的是：1)进行后GWAS分析 POAAGG研究中的全基因组显著变异，以阐明它们在这一过程中的作用 疾病，2)通过以下方式确定非洲裔美国人POAG感兴趣的其他地区 全外显子组和结构基因组学分析，以及3)评估功能 细胞模型系统中感兴趣区域的影响。我们的发现将开始定义 非洲裔美国人POAG的相关生物途径，这可能会提供 人口筛查和精确治疗的目标。

Summary Statement Primary open-angle glaucoma (POAG) represents a pressing public health problem in African Americans. This disease is the leading cause of irreversible blindness in these individuals. POAG affects African Americans more severely at earlier ages, contributing to younger generations with vision loss and adverse health and economic outcomes. Current pressure-lowering treatments for the disease have mixed success, with approximately 30% of patients still experiencing vision loss. POAG is a familial disease and there is a need for large genetic studies that elucidate disease mechanisms. This need is especially pronounced in African Americans, who, despite their increased burden of disease, remain seriously understudied. In its initial funding phase, the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study addressed this disparity by conducting the largest-ever POAG genetics study on African Americans recruited from a single city. For this renewal, we will study genetic data from a genome- wide association study of 7765 subjects and whole-exome sequencing of 8082 subjects, as well as rich phenotypic data on >90% of POAG cases. The proposed renewal will allow us to further investigate and identify variants of biologic importance to African American POAG. The aims of this study are: 1) to conduct post-GWAS analyses on genome-wide significant variants from the POAAGG study to elucidate their role in this disease, 2) to identify additional regions of interest for African American POAG through whole-exome and structural genomics analyses, and 3) to evaluate the functional impact of regions of interest in cellular model systems. Our findings will begin to define relevant biologic pathways for African American POAG, which can potentially provide targets for population screening and precision therapeutics.