Genetic variants associated with intraocular pressure in Latinos

Abstract

Purpose: Elevated intraocular pressure (IOP) is an important and modifiable risk factor for glaucoma. The identification of genetic variants associated with IOP can provide insights to the regulation of IOP and the pathogenesis of glaucoma. Here we describe a genome-wide association study (GWAS) of IOP in Latinos.

Methods: We conducted a population-based GWAS for IOP using data collected in the Los Angeles Latino Eye Study (LALES). The data were genotyped using the Illumina HumanOmniExpress Beadchip (~730K SNPs). All subjects were age 40 or older. IOP was measured by Goldmann applanation tonometry (Haag-Streit, Bern, Switzerland). The mean of left and right IOP measurements was used. When only one eye was available, the IOP measurement from the available eye was used as the surrogate for the mean. After QC, 3650 subjects remained. We used linear regression with adjustment for age, sex, and genetic ancestry.

Results: We replicated the involvement of several previously reported genetic variants, such as rs7518099 (P = 3.73 ×10^-5) within an intron of TMCO1 and rs8176743 within ABO (P = 2.95 ×10^-3). Our top locus associated with IOP is on chromosome 21q21.2 (P = 5.6 ×10^-7). Our pathways analysis also indicated candidate novel pathways for IOP.

Conclusions: Studies of genetic variants that control IOP not only offer insight to the molecular regulatory mechanism of IOP but also provide candidate genes and pathways for further investigation of glaucoma.