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: 8690069
• 负责人: Xiaoyi Raymond Gao
• 金额: $ 83.59万
• 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/8690069
• 关键词: Affect; African American; Age; American; Biological; Blindness; Caucasians; Caucasoid Race; Censuses; Complex; Control Locus; Cornea; Coupled; DNA; Data; Data Set; Databases; Detection; Diagnosis; Disease; Early Diagnosis; Electronics; Ethnic group; Etiology; Eye; Genes; Genetic; Genetic Determinism; Genome; Genotype; Glaucoma; Goals; Health Benefit; Healthcare Systems; Heterogeneity; Human; Incidence; Investigation; Knowledge; Latino; Lead; Los Angeles; Maps; Measures; Methods; Mexican Americans; Minority; Minority Groups; Nerve Degeneration; Ocular Hypertension; Optic Nerve; Participant; Pathogenesis; Pathway interactions; Phenotype; Physiologic Intraocular Pressure; Play; Population; Predisposition; Prevalence; Prevalence Study; Primary Open Angle Glaucoma; Public Health; Quality of life; Reporting; Research Personnel; Retinal Ganglion Cells; Risk; Risk Factors; Role; Sampling; Series; Testing; Therapeutic; Thick; Variant; Vision; Visual Fields; age related; base; cohort; design; effective therapy; genetic variant; genome wide association study; human disease; population based; portability; rare variant; trait

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）是最常见的青光眼，具有很强的遗传成分。POAG被认为是一组疾病，临床表现为视野丧失、视神经拔火罐和角膜中央厚度薄（CCT）等数量特征。眼压（IOP）是另一个重要的QT，常用于评估青光眼的风险。青光眼的发病机制尚不清楚。POAG的异质性对其遗传学研究提出了挑战。最近，研究人员开始利用青光眼相关的定量特征来促进青光眼致病基因的寻找。青光眼不成比例地影响墨西哥裔美国人（MAs）。虽然MAs是美国最大且增长最快的少数群体，但对MAs的基因研究却落后了。本研究的目的是确定在未充分研究的MAs中负责POAG的遗传决定因素。我们已经完成了青光眼和高眼压的完整眼科检查，并获得了洛杉矶拉丁裔眼科研究（LALES）中5338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青光眼表型组成部分相关的遗传因素。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，并根据1000基因组计划参考面板进行基因分型；开展一系列GWAS分析，以确定与POAG定量特征（如杯盘比、CCT和IOP）相关的遗传位点；确定并检验影响青光眼表型的重要途径；并在不同的种族群体中进行精细的测绘和复制研究结果。这项研究将启动青光眼变异和途径的发现，这是常见的和独特的MAs。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，并可能为这种致盲疾病提供新的检测和治疗途径。