PHILADELPHIA — Researchers at the Scheie Eye Institute, the department of Ophthalmology of the University of Pennsylvania have been awarded a five-year, $11.2 million grant from the National Institutes of Health (NIH) to study the genetic risk factors that make African Americans disproportionately more likely to develop primary open-angle glaucoma (POAG). POAG appears almost ten years earlier and progresses more rapidly in African Americans than among Caucasian individuals, making it the leading cause of irreversible blindness in this population. Approximately two million Americans suffer from this form of glaucoma.
“The goal of our study is to identify the genetic and other risk factors that underlie POAG in order to understand this increased burden of disease in African Americans,” says Joan O’Brien, MD, chair of the department of Ophthalmology in Penn’s Perelman School of Medicine, director of the Scheie Eye Institute, and primary investigator on the study.
POAG is a group of diseases that cause progressive and irreversible retinal ganglion cell damage, optic nerve degeneration, and corresponding visual field loss. Once a sufficient number of nerve cells are damaged, blind spots begin to form in the patient’s peripheral field of vision. Even when medical and surgical management are employed, retinal ganglion cell loss can be progressive and irreversible.
“We aim to understand more about the disease, its causes, and what makes African Americans more prone to developing POAG at a younger age and experiencing its most severe form,” says O’Brien. Surprisingly, researchers today still have a poor understanding of what causes POAG, which hinders early identification and focused treatment of the disease.
“We know that there is a genetic component to the disease, as family history has a strong influence,” says O’Brien. The risk of developing POAG increases tenfold when a parent or sibling has the disease, with even larger increases when an identical twin is affected. “By dissecting the disease into subtypes (called endophenotyping) and understanding the different genetic underpinnings of the disease, we can begin to develop better, more targeted treatment options.”
O’Brien will work with Scheie glaucoma specialists, Eydie Miller-Ellis, MD, Prithvi Sankar, MD, and Meredith Regina, MD, PhD, to conduct a comprehensive genetic analysis of POAG in African Americans, for which researchers at University of California, San Francisco (UCSF), will conduct the genotyping. Their genome-wide analysis will help identify the biological pathways and networks underlying the disease in 12,766 patients: 4,400 with POAG and 8,365 controls. Additional data will be provided by the Kaiser Permanente Research Program on Genes, Environment and Health, which in collaboration with UCSF has created a national resource of genetic and health data from 100,000 volunteers. Further analyses of POAG will be performed in collaboration with Kaiser, UCSF and Stanford University investigators. To date, 2,500 Philadelphia-based patients and controls have been enrolled in the study.
“Our hypothesis is that genetic variants influence the risk of POAG and the traits related to that risk, such as intraocular pressure and corneal and retinal nerve fiber layer thickness. In addition, we believe that demographic and ocular risk factors, and medical co-morbidities also contribute to the increased risk of POAG in African Americans,” says O’Brien.
“Once these genomes are analyzed in this understudied and over-affected population, the data can be used to create a risk model of POAG in African-Americans, and inexpensively re-analyzed to elucidate the genetics of other diseases that disproportionately affect this population.”
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