Age-related macular degeneration (AMD) is a condition that impacts around 200 million people globally and can lead to legal blindness. It affects a critical part of the eye (the retina) that is essential for tasks such as reading and driving.
A recent study utilizing extensive patient databases has identified genetic and demographic elements that heighten the risk of developing AMD.
Published in Nature Genetics, this research involved a team of scientists collaborating with the Million Veteran Program (MVP) from the VA Office of Research and Development. This initiative encompasses a vast biobank of veterans recruited from over 60 U.S. Department of Veterans Affairs (VA) medical centers across the country, aimed at exploring the demographic, lifestyle, clinical, and genetic risk profiles associated with AMD.
The research examined over 287,000 veterans participating in the MVP, merging these findings with data from several other independent biobanks. This effort created the largest genetic study on AMD to date, notably incorporating populations of varied ancestry.
“A significant element of our study is the inclusion of veterans of African or Hispanic descent in the MVP — groups that have not been extensively examined in prior genetic investigations of AMD,” stated Sudha Iyengar, a professor and vice chair of research in the Department of Population and Quantitative Health Sciences at Case Western Reserve University School of Medicine. “This diverse participant group is an invaluable asset for uncovering insights that could lead to new treatments for AMD, a condition with limited effective therapies currently available.”
The shared genetic makeup of all human ancestral groups showcases distinct markers that indicate a higher risk of AMD in individuals of European ancestry compared to those with African or Hispanic backgrounds.
“By enlarging the study population,” Sudha explained, “the research yielded additional insights that helped pinpoint genetic markers, even those with subtle yet potentially significant biological roles in determining whether a person may develop AMD. The investigation also increased the number of identified genes associated with AMD, growing from 34 previously recognized to 60.”
Furthermore, the research affirmed earlier findings that a history of smoking and alcohol consumption elevates the risk of developing AMD. Despite approximately 90% of MVP participants being male, the researchers validated previous observations indicating that women are more vulnerable to AMD than men.
Sudha co-led this study alongside the late Robert Igo Jr., Dana Crawford, and Jessica Cooke Bailey at the School of Medicine. They partnered with Neal Peachey, the associate chief of staff for research at the VA Northeast Ohio Healthcare System and a professor of ophthalmic research at the Cleveland Clinic Cole Eye Institute. The study received support from grants awarded to Peachey by the VA Office of Research and Development.
Scientists from various VA medical centers contributed to the study, including Bryan Gorman and Saiju Pyarajan (both from the VA Boston Healthcare System), Christopher Halladay and Wun-Shieh Wu (both from Providence VA Medical Center), and Pannos Roussos and Georgios Vodulakis (both from Mt. Sinai and Bronx VA). “They played crucial roles in integrating data from different health systems, cohorts, and data types to enhance our understanding of AMD biology,” Sudha remarked.
