UB Researchers Involved in Major Eye Disease Study

A new study of large existing patient datasets indicates genetic and demographic factors that increase the risk for developing AMD.

Two Jacobs School of Medicine and Biomedical Sciences faculty members in the Department of Ophthalmology, and a former ophthalmology resident, are co-authors on the study, which was a large, multi-center, multi-investigator consortium project.

In the study, recently published in Nature Genetics, a team of scientists worked with the Million Veteran Program (MVP) of the VA Office of Research and Development, a large biobank of veterans recruited at more than 60 U.S. Department of Veterans Affairs (VA) medical centers nationally, to examine demographic, lifestyle, clinical and genetic risk profiles for AMD.

Their study focused on more than 287,000 veterans enrolled in MVP and integrated findings with results from several other independent biobanks to define the largest study of genetic risk for AMD and the first to include populations of diverse ancestry.

“An important aspect of our study is the inclusion of veterans of African or Hispanic ancestry in the MVP — groups that have not been well studied in prior genetic studies of AMD,” says Sudha K. Iyengar, PhD, a professor and vice chair of research in the Department of Population and Quantitative Health Sciences at the Case Western Reserve University School of Medicine in Cleveland and a senior author on the paper.

“This diverse population is a unique resource to identify clues to develop therapeutics for AMD, a condition for which few effective treatments are available.”

Jacobs School faculty members Steven J. Fliesler, PhD, SUNY Distinguished Professor and Meyer H. Riwchun Endowed Chair Professor of ophthalmology; and John “Jack” M. Sullivan, MD, PhD, professor of ophthalmology, are both named co-investigators on the MVP grants that funded the research.

They each have dual appointments with the Jacobs School and the VA Western NY Healthcare System (Buffalo VA Medical Center). At the VA, Fliesler is a Research Career Scientist and director of the Ross Eye Institute Vision Research Center. Sullivan is a Staff Physician at the VA.

Along with former ophthalmology resident Matthew D. Anger, MD, they contributed data to the study, and participated in drafting, revising and finalizing the manuscript that resulted in the publication.

The collective human genome shared by all ancestral groups worldwide contains discrete signatures for higher AMD risk in those of European descent, compared to those of African or Hispanic ancestry.

“By increasing the size of the study population,” Iyengar says, “the research provided additional information to identify genetic markers with more modest but potentially important biological contributions to the likelihood that an individual will — or won’t — develop AMD. The study also found an increased number of genes linked to AMD, from 34 that were identified previously, to 60.”

The researchers also confirmed earlier beliefs that a history of smoking or alcohol use increases the likelihood of developing AMD. Although about 90% of the MVP are male enrollees, the researchers were able to confirm prior observations that women are more susceptible to AMD than men.

Iyengar co-led the research with the late Robert P. Igo Jr., PhD; Dana Crawford, PhD; and Jessica Cooke Bailey, PhD, at Case Western Reserve. They collaborated with Neal Peachey, PhD, associate chief of staff for research of the VA Northeast Ohio Healthcare System and professor of ophthalmic research at Cleveland Clinic Cole Eye Institute. The work was supported by grants to Peachey from the VA Office of Research and Development. 

The study involved scientists from several VA medical centers, including Bryan Gorman, PhD; and Saiju Pyarajan, PhD; (VA Boston Healthcare System), Christopher Halladay and Wen-Chih Wu, MD, MPH; (Providence VA Medical Center) and Panos Roussos, MD, PhD; and Georgios Voloudakis, MD, PhD; (Mt. Sinai and Bronx VA), “who played key roles in integrating data from multiple health systems, cohorts and data types to create new knowledge of AMD biology,” Iyengar says.