Glaucoma is the world’s leading cause of irreversible blindness. Primary open-angle glaucoma (POAG) is typically asymptomatic early in the disease process, and unfortunately, many are diagnosed too late to prevent vision loss.
Genome-wide association studies, which evaluate the association between genetic variants and phenotype across the genome, have mapped many genes for POAG. As well as uncovering new biology, genetic information can be combined into a polygenic risk score (PRS), which aggregates an individual’s disease risk over many genetic variants. In this nonsystematic review, performed from June 21, 2019, to October 1, 2020, we address a series of questions to explain the challenges and opportunities in translating genetic discoveries in POAG. We summarize what is known about POAG genetics and how its endophenotypes, such as intraocular pressure or cup-disc ratio, can help with prediction. We discuss the sample sizes available and how increases in the future may have an effect on the utility of prediction approaches. We explore particular scenarios, such as the use of PRS in risk stratification, and applications for individuals who are particularly high risk for POAG as a result of them carrying both a high penetrance mutation and an unfavorable PRS. Finally, we discuss the issue of equity in applying these tests and the prospects for prediction for people from various ancestry groups. The cost-effectiveness evaluation of glaucoma PRS in direct-to-consumer genetic testing and across different ancestry groups is warranted in future research.
Conclusions and Relevance
Advances in glaucoma genetics have opened the door for risk stratification based on genetic risk predictions. The PRS approach has shown good promise in predicting who will be at highest risk of POAG, which could improve outcomes if these predictions can be acted on to result in improved clinical outcomes.
Identify all potential conflicts of interest that might be relevant to your comment.
Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.
Err on the side of full disclosure.
If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.
Not all submitted comments are published. Please see our commenting policy for details.
Han X, Hewitt AW, MacGregor S. Predicting the Future of Genetic Risk Profiling of Glaucoma: A Narrative Review. JAMA Ophthalmol. Published online December 17, 2020. doi:10.1001/jamaophthalmol.2020.5404
Coronavirus Resource Center
Customize your JAMA Network experience by selecting one or more topics from the list below.
Create a personal account or sign in to: