HQ Team
January 19, 2024: A comprehensive multicohort genome-wide association study (GWAS), led by researchers at the Perelman School of Medicine at the University of Pennsylvania, has found that people of African ancestry are five times more likely to develop glaucoma and 15 times likely to be blinded by the same condition.
“Our work is an important step toward defining subgroups of glaucoma, providing the capability for early screening, and discovering targetable pathways for personalized therapeutic interventions,” said study author Rebecca Salowe, MSE, a research project manager at Penn University.
Gene variants
The research found three gene variants in people of African ancestry that make them vulnerable to this disease. More than 11,200 people of African ancestry were covered under this research. Of the three, two variants are associated with primary open-angle glaucoma (POAG), the most common form of glaucoma, which is the leading cause of irreversible blindness worldwide. Primary open-angle glaucoma occurs when the structure that normally drains fluid from the eye doesn’t work properly.
The third variant is associated with cup-to-disc ratio, a measure of glaucoma severity.
The majority of previously associated variants identified in other ancestral populations did not replicate in these African ancestry subjects, which could be tied to the genetic differences that occur in these different groups.
“Without our focus on this specific ancestry group, these unique and critical insights might have remained lost, and we would not have been able to substantially enhance our understanding of the genetics behind POAG in this overaffected population,” Shefali Verma, PhD, an assistant professor in pathology and laboratory medicine at the University of Pennsylvania, said in a statement.
“This work highlights the essential role of diversity in genetic research,” Verma said. “Without our focus on this specific ancestry group, these unique and critical insights might have remained lost, and we would not have been able to substantially enhance our understanding of the genetics behind primary open-angle glaucoma in this over-affected population.”
Genetic dataset
Previous studies pinpointed more than 170 hotspots in the genome that may fuel glaucoma — but most of the people in those studies were of European or Asian descent.
In all, this initial dataset included more than 6,000 people with glaucoma and about 5,270 people without, for comparison. The analysis turned up 46 regions of the genome linked to POAG.
The researchers then checked their results by looking at genetic data from thousands of additional people of African ancestry, as well as data from people of European or Asian descent.
“To enhance our work, we were able to identify patients in the Penn Medicine BioBank with glaucoma to validate the genetic effects we gleaned from the initial cohort we analyzed,” Ritchie said. “Without that resource, it would have been much more difficult to produce such strong work.”
The researchers also developed genetic “risk scores”—a measure of disease risk due to an individual’s genes—that outperformed a similar risk score generated with information from an analysis of individuals of European ancestry. This risk score could help patients make decisions about screening and treatment for glaucoma before it becomes a blinding illness.
This study was published in the journal Cell.