Abstract
Purpose :
Elevated intraocular pressure (IOP) is a major risk factor for glaucoma, the leading cause of irreversible blindness worldwide. IOP is also the only modifiable risk factor for glaucoma. Identifying rare variants that contribute to IOP help uncover the biological mechanisms regulating this trait, provide new therapeutic targets for IOP, and potentially glaucoma.
Methods :
We conducted this study using the recent release of 450K whole exomes from the UK Biobank. IOP measurements were obtained using the Optical Response Analyzer (Reichert Corp., Philadelphia, PA). For this study, we used corneal-compensated IOP. The average of the right and left eye IOP measurements was used for downstream analysis. A total of 110,283 study participants who have IOP measurements were included in this analysis. We performed rare-variant analyses to identify the corresponding genes associated with IOP using REGENIE with adjustment for age, sex, and the first 10 principal components of genetic ancestry.
Results :
We identified a novel gene, BOD1L1, that was significantly associated with IOP (P = 5.92 x 10-9). BOD1L1 is associated with the use of antiglaucoma preparations and miotics (P = 3.8 x 10-6). Another novel gene associated with IOP was ACAD10 (P = 1.33 x 10-10). ACAD10 is associated with glaucoma (P = 1.6 x 10-4). Further analyses may identify additional rare-variant associations with IOP.
Conclusions :
We identified novel genes and rare variants associated with IOP. Our findings provide insights into the genetics of rare variants affecting IOP.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.