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PURPOSE: 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.METHODS: 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.RESULTS: 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 locus reached genome-wide significance (P=2.88 × 10). In the FAME and MEE/RHC meta-analysis, variant rs1040227, also in the locus, was significantly associated at the genome-wide level (P=2.88 × 10) and showed nominal significance in the MEE/RHC cohort (P=0.02). In the colocalization analyses, the significant FAME GWAS locus was linked to expression regulation of this gene in six tissues including artery aorta. In gene-level analysis, also demonstrated subthreshold significance (P=6 × 10). 532 FAME and 586 MEE/RHC participants were included in the WES gene burden analysis. One gene passed false discovery rate correction for the primary outcome in FAME.CONCLUSION: 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.