Unique gene variants tied to glaucoma found in Black patients

a Black middle-aged man wearing a surgical mask sits in an examination chair in front of an optometry device as a doctor examines his eyes
The new study is a step towards understanding the genetic risks of glaucoma in people of African descent. (Image credit: FG Trade via Getty Images)

Scientists have uncovered two gene variants tied to the most common form of glaucoma by studying the population most affected by the blinding disease: People of African ancestry.

Primary open-angle glaucoma (POAG) occurs when the structure that normally drains fluid from the eye doesn't work properly. As a result, fluid builds up and damages the optic nerve, gradually leading to vision loss and potentially blindness, in severe cases. People of African ancestry have around a four to five times greater risk of experiencing POAG than those of European descent. They're also more likely to develop severe vision problems from the disease, due in part to the condition manifesting at earlier ages, on average, than is seen in those with European ancestry.

Having a family history of glaucoma is a major risk factor for the disease, meaning genetics play an influential role. 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 the new study, published Thursday (Jan. 18) in the journal Cell, researchers looked for glaucoma-related genes in the DNA of nearly 11,300 people of African descent, then confirmed the genetic risk factors in four other large datasets. To the researchers' knowledge, this is the largest study to date on the genetics of glaucoma in people of African ancestry, said senior study author Dr. Joan O'Brien, director of the Penn Medicine Center for Genetics of Complex Disease.

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"It's a very important study," said Dr. Terri Young, chair of the Department of Ophthalmology and Visual Sciences at the University of Wisconsin-Madison, who was not involved in the research. The study was well-designed and generated robust data, she told Live Science.

It is also the first comprehensive look at a demographic that's commonly excluded from genetics research but is most affected by this hereditary disease.

"That really has not been done before," Young said. "These clinicians and the patients should really be applauded."

A large portion of the study participants were enrolled through a multiyear genetics study in the greater Philadelphia area. The researchers found that partnering with a trusted Black-owned radio station — WURD Radio — helped spur enrollment. Surveyed participants often reported initial reservations about participating, due to past and current racial discrimination in the medical field. But they said they were motivated to enroll in order to access glaucoma specialists and to help improve health outcomes for other members of their community.

The team combined data from these Philadelphia residents with that of Black people from other states, as well as Africans from Nigeria and Ghana. 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. In these analyses, three gene variants popped up as being the most important for POAG in people of African ancestry.

"Two of those were entirely novel," meaning they'd never been linked to glaucoma before, O'Brien told Live Science.

The researchers ran some early experiments to start to unravel how these genes affect the eye's function or structure, but on that front, there's more work to do, Young said. Future work could probe the function of these genes in different tissues of the eye in lab dishes, as well as in animal models of glaucoma, she said.

The researchers also developed genetic "risk scores" intended to flag people with raised odds of developing glaucoma. They trained one risk score-generator on data from people of African ancestry and another on people of European ancestry — compared with the latter, the former was much more accurate at predicting when a person of African descent had glaucoma.

In the future, risk scores like these could help pinpoint which patients need to initiate or adjust their monitoring or treatment plans for glaucoma, ensuring they get treated promptly if they do develop the disease, Young said. Better understanding the genetic profile of people with glaucoma could also lead to better, more-tailored treatments, she added. 

POAG often leads to elevated pressure inside the eye, which can damage the optic nerve. Current treatments, such as eye drops and surgery, are aimed at relieving that pressure, but some people still lose their sight after starting treatment. Plus, some people with POAG have normal eye pressure but still lose vision.

"So pressure alone is our only treatment, but pressure alone is not sufficient to address the problems associated with this disease," O'Brien told Live Science. The new genetic study helps lay the groundwork for scientists to uncover new glaucoma treatments.

Editor's note: This article was updated at 1:30 p.m. on Jan. 18, 2024 to clarify a quote from Dr. Terri Young.

This article is for informational purposes only and is not meant to offer medical advice.

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Nicoletta Lanese
Channel Editor, Health

Nicoletta Lanese is the health channel editor at Live Science and was previously a news editor and staff writer at the site. She holds a graduate certificate in science communication from UC Santa Cruz and degrees in neuroscience and dance from the University of Florida. Her work has appeared in The Scientist, Science News, the Mercury News, Mongabay and Stanford Medicine Magazine, among other outlets. Based in NYC, she also remains heavily involved in dance and performs in local choreographers' work.