Abstract
Purpose :
The retinal pigment epithelium (RPE) is a monolayer of pigmented cells in the outer retina. The RPE has numerous critical roles in retinal physiology, and RPE dysfunction is associated with retinal diseases including age-related macular degeneration. In this study, we sought to perform a genome-wide association study of RPE thickness and to utilize this data to identify the determinants of RPE thickness and to observe the relationships between RPE thickness and other pigmentation-related phenotypes.
Methods :
Overall RPE thickness values for the left and right eye were derived from high-quality optical coherence tomography (OCT) scans of 31,225 UK Biobank subjects. REGENIE was utilized to perform GWAS. Lead variants were investigated for associations with pigmentation-related traits using Phenoscanner. Causal determinants of RPE thickness were identified using a phenome-wide Mendelian randomization approach. The genetic correlation between RPE thickness and other pigmentation-related traits was assessed.
Results :
We identified 16 loci associated with left eye RPE thickness and 15 loci associated with right eye RPE thickness. Overlap between single nucleotide variants (SNVs) associated with RPE thickness and other pigmentation traits were identified. The leading SNV (rs1126809, TYR) is known to be associated with several pigmentation traits including skin color, iris color, the tendency to tan, and retinal pigmentation; as well as being implicated in skin cancers. Mendelian randomization indicated that AMD and lipid metabolism are associated with RPE thickness.
Conclusions :
This study has identified genetic variants associated with RPE thickness, supports a relationship between RPE thickness and other pigmentation-related traits, and reinforces recognized relationships between lipids and RPE physiology.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.