A larger genetic data set sharpens glaucoma risk prediction
Researchers at QIMR Berghofer, Flinders University and international collaborating institutions have developed a genetic test intended to identify people at markedly elevated risk of open-angle glaucoma, the most common form of glaucoma and a leading cause of irreversible blindness worldwide.
The test is based on a polygenic risk score: a single measurement that combines the small effects of millions of genetic variations associated with disease risk. According to the researchers, the updated score was constructed using genetic data from more than six million people, including almost 300,000 people with glaucoma.
That scale distinguishes the new work from an earlier version of the tool published in 2020, which was based on roughly 8,000 glaucoma cases. The study, published in Ophthalmology, reports a substantial increase in predictive performance from the larger data set.
Why earlier identification matters
Glaucoma damages the optic nerve, often without noticeable symptoms at its earliest stages. Vision that has already been lost cannot be restored, making early detection and timely treatment central to preventing avoidable impairment.
Yet diagnosis remains a major challenge. The researchers note that about half of people with glaucoma are undiagnosed, including in countries with good access to eye care. A tool that separates people with ordinary population-level risk from those who may benefit from earlier or more frequent assessment could therefore be useful alongside established eye examinations.
The new score is not presented as a diagnosis. Instead, it is a way of estimating inherited susceptibility. Clinical decisions would still require eye-care assessment and consideration of other factors, but a more informative estimate of risk could help direct attention before symptoms or permanent sight loss appear.
What the study found
In Australians of European ancestry, people in the highest 10% of genetic risk were reported to be 10 times more likely to have glaucoma than everyone else. The previous version of the score identified an approximately fourfold increase in risk for its highest-risk group.
The study also found a large difference in the age at which disease developed. On average, people in the highest 10% of genetic risk developed glaucoma about 25 years earlier than those in the lowest 10%.
The researchers provided one illustration of the practical difference. A healthy 65-year-old of European ancestry in the highest 20% of genetic risk had an estimated 10% chance of developing glaucoma during the following decade. For a person in the lowest 20%, the comparable estimate was 0.4%.
Beyond identifying who may develop glaucoma, the score also helped predict disease severity. In a long-term study involving people with suspected or early glaucoma, the highest-risk group had a greater need for treatment. That finding suggests genetic risk information could eventually help clinicians distinguish between people whose condition is likely to remain less threatening and those who may need closer follow-up.
Potential role in screening
The central promise of the approach is better targeting. Rather than applying the same screening intensity to everyone, health systems could potentially use genetic information to identify people who should begin eye checks earlier or attend them more frequently.
That may be particularly valuable for a disease that commonly progresses silently. Many people do not know they have glaucoma until damage has already accumulated, and the opportunity to preserve vision is greatest before that point.
Lead researcher Stuart MacGregor said the expanded data set produced a significant improvement in predictive accuracy. He described the result as the strongest genetic risk prediction reported for a common complex disease, based on the study’s findings.
Important limits before clinical rollout
The reported estimates in the source material specifically refer to Australians of European ancestry. That matters because genetic prediction tools can perform differently across populations, depending on the data used to develop and validate them. Further work will be needed to establish how reliably the score performs in other ancestry groups and health-care settings.
There are also practical questions about how a genetic score should be incorporated into routine care, who should receive testing, and how clinicians should communicate results. A higher score indicates greater inherited risk; it does not establish that a person has glaucoma or that vision loss is inevitable.
Still, the study points toward a more proactive model of glaucoma prevention. By combining genetic risk with clinical assessment, researchers hope to find people most likely to develop disease before its quiet early stages give way to irreversible damage.
This article is based on reporting by Medical Xpress. Read the original article.
Originally published on medicalxpress.com
