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Epiretinal membrane (ERM) is a common retinal condition characterized by the presence of fibrocellular tissue on the retinal surface, often with visual distortion and loss of visual acuity. We studied European American (EUR), African American (AFR), and Latino (admixed American, AMR) ERM participants in the Million Veteran Program (MVP) for genome-wide association analysis-a total of 38,232 case individuals and 557,988 control individuals. We completed a genome-wide association study (GWAS) in each population separately, and then results were meta-analyzed. Genome-wide significant (GWS) associations were observed in all three populations studied: 31 risk loci in EUR subjects, 3 in AFR, and 2 in AMR, with 48 in trans-ancestry meta-analysis. Many results replicated in the FinnGen sample. Several GWS variants associate to alterations in gene expression in the macula. ERM showed significant genetic correlation to multiple traits. Pathway enrichment analyses implicated collagen and collagen-adjacent mechanisms, among others. This well-powered ERM GWAS identified novel genetic associations that point to biological mechanisms for ERM., Competing Interests: Declaration of interests J.G. is named as an inventor on PCT patent application #15/878,640 entitled “Genotype-guided dosing of opioid agonists,” filed January 24, 2018, and issued on January 26, 2021, as US Patent No. 10900082. J.G. is paid for editorial work for the journal Complex Psychiatry (Karger). D.E. is an ad hoc consultant for Alcon, Dutch Ophthalmic, GelMEDIX, and Genentech; reports research funding from Neurotech and Unity Biotechnology; is a member of the Advisory Board and Stockholder for InGel Therapeutics, Pykus Therapeutics, and RetMap; reports being Advisor, Patents, Royalties, and Stockholder in Aldeyra Therapeutics; and is a member of the Data Safety Monitoring Board for Asclepix. M.B.S. has in the past 3 years received consulting income from Acadia Pharmaceuticals, Aptinyx, atai Life Sciences, BigHealth, Bionomics, BioXcel Therapeutics, Boehringer Ingelheim, Clexio, Eisai, EmpowerPharm, Engrail Therapeutics, Janssen, Jazz Pharmaceuticals, NeuroTrauma Sciences, PureTech Health, Sumitomo Pharma, and Roche/Genentech. M.B.S. has stock options in Oxeia Biopharmaceuticals and EpiVario. He has been paid for his editorial work on Depression and Anxiety (Editor-in-Chief), Biological Psychiatry (Deputy Editor), and UpToDate (Co-Editor-in-Chief for Psychiatry). He is on the scientific advisory board for the Brain and Behavior Research Foundation and the Anxiety and Depression Association of America., (Published by Elsevier Inc.)