{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T09:22:37Z","timestamp":1767691357041,"version":"3.48.0"},"posted":{"date-parts":[[2026,1,2]]},"group-title":"Ophthalmology","reference-count":48,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>To identify genetic variants associated with glucocorticoid (GC)-induced intraocular pressure (IOP) change using genome-wide association study (GWAS) and whole exome sequencing (WES) analyses.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>530 participants from the Fluocinolone Acetonide in Diabetic Macular Edema (FAME) trials were analyzed, with replication performed in an independent cohort of 588 participants from the Mass Eye and Ear\/Retina Health Center (MEE\/RHC). All participants were exposed to GC, primarily via intravitreal injection. IOP was measured at baseline and serially within 6 months following GC exposure. GWAS and rare variant gene burden analyses were applied, adjusting for covariates.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Genetic associations for maximal IOP change within 6 months after GC exposure were evaluated. For the primary outcome across all ancestries in FAME, one variant, rs13425173 within the\n                    <jats:italic>UBE2E3<\/jats:italic>\n                    locus reached genome-wide significance (P=2.88 X 10\n                    <jats:sup>-8<\/jats:sup>\n                    ). In the FAME and MEE\/RHC meta-analysis, variant rs1040227, also in the\n                    <jats:italic>UBE2E3<\/jats:italic>\n                    locus, was significantly associated at the genome-wide level (P=2.88 X 10\n                    <jats:sup>-8<\/jats:sup>\n                    ) and showed nominal significance in the MEE\/RHC cohort (P=0.02). In the colocalization analyses, the significant FAME GWAS\n                    <jats:italic>UBE2E3<\/jats:italic>\n                    locus was linked to expression regulation of this gene in six tissues including artery aorta. In gene-level analysis,\n                    <jats:italic>UBE2E3<\/jats:italic>\n                    also demonstrated subthreshold significance (P=6 X 10\n                    <jats:sup>-6<\/jats:sup>\n                    ). 532 FAME and 586 MEE\/RHC participants were included in the WES gene burden analysis. One gene\n                    <jats:italic>, MSTO1,<\/jats:italic>\n                    passed false discovery rate correction for the primary outcome in FAME.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>We have identified genome-wide significant common variants associated with GC-IOP change, as well as genes and rare variants that may influence GC-induced IOP change.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2025.12.31.25343232","type":"posted-content","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T01:00:18Z","timestamp":1767402018000},"source":"Crossref","is-referenced-by-count":0,"title":["Genome-Wide Association Study for Glucocorticoid-Induced Ocular Hypertension"],"prefix":"10.64898","author":[{"given":"Jyoti","family":"Lama","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renee","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia","family":"Huerta-Chagoya","sequence":"additional","affiliation":[{"name":"Program in Metabolism Broad Institute of MIT and Harvard, Cambridge, MA"},{"name":"Center for Genomic Medicine and Diabetes Unit, Endocrine Division, Department of Medicine, Massachusetts General Hospital, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie","family":"Huynh","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynn K.","family":"Stanwyck","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weilin","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ananya","family":"Mukundan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janine Y.","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gayatri","family":"Susarla","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delia","family":"Sang","sequence":"additional","affiliation":[{"name":"Delia N. Sang, MD, Brookline, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"George N.","family":"Papaliodis","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucy Q.","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"Rossin","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA"},{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Elkins","sequence":"additional","affiliation":[{"name":"Retina Health Center, Fort 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