Genetic Risk and OCT-Based Phenotypic Associations in Age-Related Macular Degeneration

The risk for developing age-related macular degeneration (AMD) is associated with multiple genetic variants. We aim to evaluate the association of AMD genetic risk variants with specific features of the disease detected by OCT.

A retrospective cross-sectional study.

Subjects diagnosed with AMD and healthy controls (>50 years of age) from a single tertiary referral center.

Genotyping of 52 single nucleotide polymorphisms associated with AMD was analyzed in 578 patients. Weighted genetic risk scores (WGRSs) were calculated for variants in genes encoding proteins involved in the complement cascade, lipid metabolism, and other pathways, respectively. A global WGRS was calculated for all 52 variants. OCT images were annotated for the presence of typical drusen, subretinal drusenoid deposits, hyperreflective foci (HRF), complete retinal pigmented epithelium and outer retinal atrophy (cRORA), and macular neovascularization.

Association of WGRS and individual genetic risk variants with specific disease features detected by OCT.

A positive correlation between the presence of drusen and the lipid WGRS was detected (r = 0.09, P = 0.02). Logistic regression analysis indicated associations between cRORA and the complement score (odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.05-1.50; P = 0.01), as well as the global score (OR = 1.29, 95% CI 1.13-1.46; P < 0.001). Regression also showed an association of HRF with the age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase 1 variant (OR = 1.53, 95% CI 1.03-2.27; P = 0.03), the other pathways score (OR = 1.94, 95% CI 1.20-3.12; P = 0.007), and the global score (OR = 1.16, 95% CI 1.00-1.35; P = 0.04).

Weighted genetic risk scores based on risk variants for AMD are associated with specific disease features. Tighter association of the global WGRS compared to pathway-specific scores suggests that several pathways are involved in the development of specific disease features such as cRORA, drusen, and HRF.

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