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YSM, VA Researchers Complete First Genome-Wide Association Study of Epiretinal Membrane

June 12, 2024

VA Connecticut Healthcare Center and Yale School of Medicine researchers have completed the first well-powered, genome-wide association study of epiretinal membrane (ERM), a common retinal disorder — also known as macular pucker -- that often causes visual distortion or loss of visual acuity. For symptomatic epiretinal membrane, eye surgery — vitrectomy with epiretinal membrane peeling -- is the typical treatment.

The scientists used data from the U.S. Department of Veterans Affairs Million Veteran Program, which looks at how genes, lifestyle, military experiences, and exposures affect health and wellness in veterans. They identified 31 independent risk loci in European-ancestry participants, three in African-ancestry, and two in Latino participants.

A trans-ancestry meta-analysis revealed 48 independent risk loci, highlighting shared biology between populations. Several associated loci were previously linked to ocular phenotypes or body mass index-related traits, and many of the findings were independently replicated in a sample gathered by FinnGen, a large-scale genome research collaboration based in Finland. ERM showed significant genetic relationships to multiple traits, including depression.

The study, published in Cell Genomics, also investigated the functional consequences of the identified variants through expression quantitative trait loci analysis, transcriptome-wide association study, and pathway enrichment analysis. These analyses implicated genes and pathways relevant to epiretinal membrane pathophysiology, such as collagen pathways.

The authors discussed the potential biological mechanisms underlying the identified associations and the importance of studying diverse populations in genome-wide association studies.

"We were able to expand analysis to include groups which are currently underrepresented in genetic studies,” said co-author Daniel Levey, PhD, assistant professor of psychiatry. “We were able to be more inclusive due to the efforts of the VA Million Veteran Program. It’s crucial that diverse participants are included in these kinds of analyses to ensure equitable access to the potential benefits of this kind of research.”

“This well-powered study provides novel insights into the genetic architecture of epiretinal membrane and lays the foundation for future research into its pathophysiology and potential therapeutic targets,” said author Joel Gelernter, MD, Foundations Fund Professor of Psychiatry and professor of genetics and of neuroscience. Gelernter is director of the Yale Department of Psychiatry’s Division of Human Genetics.

Yale co-authors include Marco Galimberti, Hang Zhou, Keyrun Adhikari and Priya Gupta.

The research was supported primarily by funding from the U.S. Department of Veterans Affairs.

Submitted by Christopher Gardner on June 12, 2024