A Human Pharmacogenomics Approach Provides Insight Into the Pathogenesis and Pathophysiology of Steroid-Induced Ocular Hypertension.

Purpose: To identify single nucleotide polymorphisms (SNPs) and their likely target genes associated with steroid-induced ocular hypertension (SI-OHT), and to conduct functional annotation analyses. Design: Genome-wide association study (GWAS). Participants: Patients with Fuchs endothelial corneal dystrophy were enrolled after corneal transplantation at a single clinical practice (N = 439 Methods: Saliva samples were collected, and DNA was extracted and genotyped. A GWAS was then conducted, with maximum change in IOP serving as the quantitative trait (QT). Replication analysis employed 4 independent cohorts (N = 49-103) with participants that had been previously genotyped. Main Outcome Measures: Linear regression analysis was performed to determine association between QT and genotype using the Haplotype Reference Consortium reference panel for imputation. Results: A total of 46 SNPs of genome-wide significance ( Conclusions: Why some individuals develop SI-OHT, but others do not, has remained unknown since glucocorticoids were first used to treat eye disease in the early 1950s. Results of this study demonstrate a genetic basis for SI-OHT, support a relationship with other high-tension OHT phenotypes, and provide hypothesis-generating information for laboratory follow-up. Discovered and replicated SNPs may be valuable for SI-OHT risk prediction and prioritized target genes might be targeted for SI-OHT management. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.