Mexican American Glaucoma Genetic Study (MAGGS)

描述(申请人提供)：青光眼是导致不可逆性失明的主要原因，对数百万美国人的生活质量有重大影响。原发性开角型青光眼(POAG)是青光眼中最常见的一种，具有很强的遗传成分。POAG被认为是一组疾病，临床上以多个数量性状(QTS)为特征，如视野丧失、视神经拔罐和中央角膜厚度(CCT)变薄。眼内压(IOP)是另一个重要的QT，常被用来评估青光眼的风险。青光眼的发病机制尚不清楚。POAG的异质性对其遗传学研究的努力提出了挑战。最近，研究人员开始使用与青光眼相关的量化特征来促进青光眼致病基因的寻找。青光眼对墨西哥裔美国人的影响不成比例。虽然MA是美国最大且增长迅速的少数群体，但MA的基因研究一直落后。这项研究的目的是确定在未被研究的MA中导致POAG的遗传决定因素。我们已经完成了针对青光眼和高眼压的完整眼科检查，并获取了5338名洛杉矶拉丁人眼科研究(LALES)参与者的DNA。我们将使用全基因组关联研究(Gwas)来确定与MAS中青光眼表型成分相关的遗传因素。我们的具体目标是：使用Illumina OmniExpress和新开发的HumanExome BeadChips对5,338名参与者进行基因分型，并基于1000基因组计划参考小组进行基因分型；开展一系列Gwas分析，以确定与POAG的定量特征相关的遗传基因座，如杯盘比、CCT和眼压；确定和测试影响青光眼表型的重要途径；以及进行精细图谱绘制，并在不同种族之间复制结果。这项研究将开始发现青光眼的变异和途径，这是常见的和独特的多发性硬化。此外，从这项研究中获得的知识将扩大我们对青光眼的理解，并可能为这种致盲疾病提供新的检测和治疗途径。

DESCRIPTION (provided by applicant): Glaucoma is a leading cause of irreversible blindness and has a substantial impact on the quality of life of millions of Americans. Primary open angle glaucoma (POAG) is the most common form of glaucoma and has a strong genetic component. POAG is regarded as a group of disorders and is clinically characterized by several quantitative traits (QTs), such as visual field loss, optic nerve cupping and thin central corneal thickness (CCT). Intraocular pressure (IOP) is another important QT that is often used to assess the risk of developing glaucoma. The pathogenesis of glaucoma is not well understood. The heterogeneity of POAG has challenged the efforts of its genetic investigations. Recently, researchers have begun to use the quantitative features associated with glaucoma to facilitate the search for glaucoma disease-causing genes. Glaucoma disproportionately affects Mexican Americans (MAs). While MAs are the largest and fast growing minority group in the US, genetic studies in MAs have lagged behind. The goal of this study is to identify genetic determinants responsible for POAG in the understudied MAs. We have finished a complete ophthalmologic examination for glaucoma and ocular hypertension and obtained DNA on 5,338 participants in the Los Angeles Latino Eye Study (LALES). We will use a genome-wide association study (GWAS) to identify genetic factors related to components of the glaucoma phenotype in MAs. Our specific aims are: to genotype the 5,338 participants using the Illumina OmniExpress and newly developed HumanExome BeadChips and impute genotypes based on the 1000 Genomes Project reference panels; to carry out a series of GWAS analyses to identify genetic loci associated with the quantitative features of POAG, e.g. cup-to-disc ratio, CCT and IOP; to identify and test significant pathways influencing the glaucoma phenotype; and to carry out fine mapping and replicate findings among different ethnic groups. This study will initiate the discovery of glaucoma variants and pathways that are common and unique to MAs. Furthermore, the knowledge derived from this study will extend our understanding of glaucoma and may potentially suggest new detection and therapeutic avenues for this blinding disease.