Mexican American Glaucoma Genetic Study (MAGGS)

墨西哥裔美国人青光眼遗传学研究 (MAGGS)

• 批准号: 8607661
• 负责人: Xiaoyi Raymond Gao
• 金额: $ 90.62万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-30 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8607661
• 关键词: Mexican; American; Glaucoma; Genetic; Study

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.

描述（由申请人提供）：青光眼是导致不可逆失明的主要原因，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）是青光眼最常见的形式，具有很强的遗传成分。POAG被认为是一组疾病，其临床特征是几个数量性状（QT），如视野丧失、视神经杯状和薄的中央角膜厚度（CCT）。眼内压（IOP）是另一个重要的QT，通常用于评估青光眼的风险。青光眼的发病机制尚不清楚。POAG的异质性给其遗传学研究带来了挑战。最近，研究人员已经开始使用与青光眼相关的定量特征来促进青光眼致病基因的搜索。青光眼不成比例地影响墨西哥裔美国人（MA）。虽然MA是美国最大且增长迅速的少数群体，但MA的遗传研究却落后于人。本研究的目的是确定遗传因素负责POAG在欠研究的MA。我们完成了对青光眼和高眼压症的全面眼科检查，并获得了洛杉矶拉丁裔眼科研究（LALES）5,338名参与者的DNA。我们将使用全基因组关联研究（GWAS）来确定与MAs中青光眼表型组分相关的遗传因素。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个基因组计划参考组进行基因型插补;进行一系列GWAS分析以鉴定与POAG的定量特征相关的遗传基因座，例如杯盘比、CCT和IOP;鉴定并测试影响青光眼表型的重要途径;并在不同民族群体中进行精细绘图和复制调查结果。这项研究将开始发现青光眼的变异和途径是共同的和独特的MA。此外，从这项研究中获得的知识将扩展我们对青光眼的理解，并可能为这种致盲性疾病提供新的检测和治疗途径。