10 Years of GWAS in intraocular pressure

Abstract

Intraocular pressure (IOP) is the only modifiable risk factor for glaucoma, the leading cause of irreversible blindness worldwide. In this review, we summarize the findings of genome-wide association studies (GWASs) of IOP published in the past 10 years and prior to December 2022. Over 190 genetic loci and candidate genes associated with IOP have been uncovered through GWASs, although most of these studies were conducted in subjects of European and Asian ancestries. We also discuss how these common variants have been used to derive polygenic risk scores for predicting IOP and glaucoma, and to infer causal relationship with other traits and conditions through Mendelian randomization. Additionally, we summarize the findings from a recent large-scale exome-wide association study (ExWAS) that identified rare variants associated with IOP in 40 novel genes, six of which are drug targets for clinical treatment or are being evaluated in clinical trials. Finally, we discuss the need for future genetic studies of IOP to include individuals from understudied populations, including Latinos and Africans, in order to fully characterize the genetic architecture of IOP.

Keywords: ExWAS; GWAS; Mendelian randomization; intraocular pressure; polygenic risk score; underrepresented population.

FIGURE 1

Number of novel intraocular pressure loci and study sample size in the last 10 years. Genetic association studies for IOP published in the past 10 years are represented by either (a) a circle for GWAS or (b) a star for ExWAS. The x-axis shows the year the study was published, and the y-axis shows the sample size of the study. The color and size of each plotted icon are proportional to the total number of loci and the number of novel loci discoveries that were reported in the corresponding study, respectively.