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.
Glaucoma disproportionately affects Mexican Americans, the most populous minority population in the US. However, the genetic factors contributing to this increased susceptibility are poorly understood. This study will have significant public health benefits by identifying variants, genes and pathways associated with glaucoma, thereby potentially leading to early detection and effective treatment of this blinding disease.
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| Nannini, Drew; Torres, Mina; Chen, Yii-Der I et al. (2016) Reply. Ophthalmology 123:e31-2 |
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