Primary open angle glaucoma (POAG) is a leading cause of blindness. This disease disproportionately affects African Americans, who have a four- to five-fold higher risk of disease than age-matched Caucasians. In addition to its high prevalence, the risk of blindness from glaucoma in African Americans is more than 10 times greater than Caucasians, making it the leading cause of blindness in African Americans. The goal of this study is to identify common genes that are responsible for idiopathic Primary Open Angle Glaucoma in the understudied African American population. Whole genome association (WGA) has recently met with dramatic success in the analysis of complex diseases, including the identification of Complement Factor H as the strongest genetic risk factor for age- related macular degeneration. These methods typically utilize hundreds of thousands of genetic markers to conduct case-control association tests on genes across the entire human genome. These methods have not been applied to glaucoma in African Americans because of the extremely high cost, and because of the difficulty of assembling the necessary dataset: historical research abuses have made many potential African American controls reluctant to participate in medical research. Both of these difficulties can be addressed through the use of a new whole genome association technique call admixture mapping. Admixture mapping is a whole-genome association technique that takes advantage of the unique genetic structure of admixed populations such as African Americans. It has recently been used to successfully map genes for multiple sclerosis and prostate cancer. Admixture mapping is 4-5 times less expensive per sample than other forms of whole-genome association because it requires many fewer markers while retaining similar power to detect disease-associated susceptibility variants. Further, this technique uses only African American cases and does not require matching controls, thus enabling a highly powered initial genome scan. Follow-up to the genome scan will be performed in a large POAG case/control dataset collected in Ghana, West Africa. The identification of glaucoma susceptibility genes in African Americans could lead to improved treatment methods for this severely affected and understudied population.

Public Health Relevance

Glaucoma is especially common and severe in African Americans. We are using a new genetic technique to find genes that contribute to glaucoma in this population. Finding such genes could prevent blindness by leading to better treatments for the disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY019126-03
Application #
7906646
Study Section
Anterior Eye Disease Study Section (AED)
Program Officer
Chin, Hemin R
Project Start
2008-09-01
Project End
2013-08-31
Budget Start
2010-09-01
Budget End
2011-08-31
Support Year
3
Fiscal Year
2010
Total Cost
$548,440
Indirect Cost
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Khawaja, Anthony P; Cooke Bailey, Jessica N; Wareham, Nicholas J et al. (2018) Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma. Nat Genet 50:778-782
Bailey, Jessica N Cooke; Gharahkhani, Puya; Kang, Jae H et al. (2018) Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets. Invest Ophthalmol Vis Sci 59:629-636
Liu, Yutao; Allingham, R Rand (2017) Major review: Molecular genetics of primary open-angle glaucoma. Exp Eye Res 160:62-84
Pasquale, Louis R (2016) Vascular and autonomic dysregulation in primary open-angle glaucoma. Curr Opin Ophthalmol 27:94-101
Khawaja, Anthony P; Cooke Bailey, Jessica N; Kang, Jae Hee et al. (2016) Assessing the Association of Mitochondrial Genetic Variation With Primary Open-Angle Glaucoma Using Gene-Set Analyses. Invest Ophthalmol Vis Sci 57:5046-5052
Hauser, Michael A; Aboobakar, Inas F; Liu, Yutao et al. (2015) Genetic variants and cellular stressors associated with exfoliation syndrome modulate promoter activity of a lncRNA within the LOXL1 locus. Hum Mol Genet 24:6552-63
Li, Zheng; Allingham, R Rand; Nakano, Masakazu et al. (2015) A common variant near TGFBR3 is associated with primary open angle glaucoma. Hum Mol Genet 24:3880-92
Kang, J H; Loomis, S J; Yaspan, B L et al. (2014) Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma. Eye (Lond) 28:662-71
Springelkamp, Henriët; Höhn, René; Mishra, Aniket et al. (2014) Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. Nat Commun 5:4883
Li, Yi-Ju; Minear, Mollie A; Qin, Xuejun et al. (2014) Mitochondrial polymorphism A10398G and Haplogroup I are associated with Fuchs' endothelial corneal dystrophy. Invest Ophthalmol Vis Sci 55:4577-84

Showing the most recent 10 out of 39 publications