NEI funded researchers identify 133 genetic variants that predict glaucoma risk

picture of visual field obscured at periphery
Glaucoma (NEI)

Results inform strategies aimed at preventing vision loss

From the National Eye Institute

Researchers funded by the National Eye Institute (NEI) have identified 133 genetic variants that predict with 75-percent accuracy a person’s risk for developing glaucoma related to elevated pressure within the eye. Future genetic tests could identify high-risk individuals who would benefit from early interventions aimed at preventing vision loss from glaucoma, a leading cause of vision loss and blindness in the United States. The study appeared May 21 in Nature Genetics. NEI is part of the National Institutes of Health.

“That level of accuracy is not perfect, but it’s a significant improvement over our current ability to predict a person’s risk for glaucoma,” said the study’s co-author Janey Wiggs, M.D., Ph.D., associate chief of ophthalmology clinical research at Massachusetts Eye and Ear, Boston. In its early stages, glaucoma causes peripheral vision loss, which often progresses unnoticed. Without timely detection and treatment, the disease can cause blindness. Knowing their genetic status, individuals at high-risk could have their eye pressure closely monitored and pressure-lowering therapies could be administered at the earliest stages of disease. “Substantial evidence shows that the earlier you treat people, the better they are going to do in terms of maintaining and preserving useful vision,” Wiggs said.

To identify the genetic variants, the researchers first compared intraocular pressure (IOP) readings and genotype data from 139,555 participants across three large groups of people. All participants were of European descent. The analysis revealed 133 genetic variants associated with the risk of elevated IOP. Among the 133 variants identified, 68 had not been previously linked to IOP. Many of the loci point to cellular processes, such as lipid metabolism and mitochondrial function, that contribute to intraocular pressure.

Next, the researchers sought to identify which of the variants that elevate IOP truly were associated with an increase in glaucoma risk. The researchers determined the relevance of the variants using the NEIGHBORHOOD glaucoma consortium data, which represents a population of 4000 people with glaucoma and 30,000 people without. Funded by the NEI, the NEIGHBORHOOD glaucoma consortium is the largest, most thoroughly characterized population of people with known glaucoma status.

“Unexpectedly, we found an almost direct correlation between the magnitude of the genetic variants’ effect on eye pressure and their effect on glaucoma risk. In other words, IOP appears to be the overriding factor that determines whether someone develops glaucoma,” Wiggs said.

“These genetic loci will guide future studies aimed at elucidating the cellular pathways associated with glaucoma,” said Neeraj Agarwal, Ph.D., program director of translational research at NEI.

Future studies will determine whether the genetic variants can predict age of onset, severity, and other disease characteristics. For example, people with certain genetic variants may be more likely to develop glaucoma between ages 20 to 40 as opposed to the typical onset age of 70 to 80. Other variants appear to be associated with very high intraocular pressure and lipid metabolism abnormalities that affect cholesterol levels. “We do not yet understand the connection between high intraocular pressure and cholesterol metabolism, but this potential link suggests that these patients might benefit from a systemic approach to targeting lipids,” Wiggs said.

The study was an international collaboration among researchers in the United States, United Kingdom, and Singapore. The investigation was funded in part by NEI grants R01EY022305, P30EY014104 and HG005259-01.


Khawaja, AP et al. “Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma.” May 21, 2018. Nature Genetics. doi:10.1038/s41588-018-0126-8.


This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process— each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

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