Polygenic Risk Score and Rare Variant Burden Identified by Targeted Sequencing in a Group of Patients with Pigment Epithelial Detachment in Age-Related Macular Degeneration

Abstract

A subset of ophthalmic imaging examination results from 334 patients were subjected to reanalysis to identify a specific group of patients with pigment epithelial detachment (PED) in at least one eye. Overall, we found a subgroup of 47 patients manifesting PED and studied their genotypes in comparison to those of patients with age-related macular degeneration without PED and healthy controls. We established a polygenic risk score that allowed the explanation of 16.3% of the variation within the disease. The highest predictive value was achieved for a model consisting of six non-coding variants: rs760306 (BEST1), rs148662546 (BEST1), rs11569560 (C3), rs74600252 (GUCA1B), rs2240688 (PROM1), and rs185507582 (TCF4). The risk of PED occurrence was found to be the highest in the first tercile, showing a 7.89-fold higher risk compared to the third tercile for AMD without PED (95% CI: 2.87; 21.71, p < 0.001) and a 7.22-fold higher risk compared to the healthy controls (95% CI: 2.60; 20.06, p < 0.001). In addition, we focused on rare variants in targeted genes. The rare variants’ burden was compared among the groups, but no statistical significance was observed in the number of rare variants, predicted functional effects, or pathogenicity classification.

Association of Genetic Risk for Age-Related Macular Degeneration with Morphological Features of the Retinal Microvascular Network

“…PRS is of interest to researchers in relation to many diseases, and, due to the polygenic basis of many diseases, it is used as an important indicator in numerous scientific studies in many specializations [36,[40][41][42]. PRS in the group presented is described in our previous publications, where the detailed genetic testing process is described [30]. Sekimitsu et al conducted a rare study examining the correlation between retinal OCT images and PRS, with a focus on evaluating the risk of cognitive impairment [39].…”

“…In this study, data from a subgroup of subjects, previously considered by W ąsowska et al, were used in the PRS calculation using PLINK for QC of genotyped data and the additive model available via PRSice2 software (version 2.3.5). The PRS study was performed on the Polish population based on the targeted sequencing data involving the enrichment of genes known to be associated with AMD at the time of the study [30].…”