Genetic and environmental risk factors for reticular pseudodrusen in the EUGENDA study

• Published in: Molecular vision Vol. 27; pp. 757 - 767
• Main Authors: Altay, Lebriz, Liakopoulos, Sandra, Berghold, Aileen, Rosenberger, Kerstin-Daniela, Ernst, Angela, de Breuk, Anita, den Hollander, Anneke I, Fauser, Sascha, Schick, Tina
• Format: Journal Article
• Language: English
• Published: United States Molecular Vision 2021
• Subjects: Case-Control Studies; Complement Factor H - genetics; Humans; Macular Degeneration - complications; Macular Degeneration - epidemiology; Macular Degeneration - genetics; Polymorphism, Single Nucleotide; Prospective Studies; Proteins - genetics; Retinal Drusen - complications; Retinal Drusen - genetics; Risk Factors; Tomography, Optical Coherence
• ISSN: 1090-0535; 1090-0535

The purpose of this study was to analyze genetic and nongenetic associations with reticular pseudodrusen (RPD) in patients with and without age-related macular degeneration (AMD). This case-control study included 2,719 consecutive subjects from the prospective multicenter European Genetic Database (EUGENDA). Color fundus photographs and optical coherence tomography (OCT) scans were evaluated for the presence of AMD and RPD. Association of RPD with 39 known AMD polymorphisms and various nongenetic risk factors was evaluated. Stepwise backward variable selection via generalized linear models (GLMs) was performed based on models including the following: a) age, sex, and genetic factors and b) all predictors. Receiver operating characteristic (ROC) curves and the areas under the curve (AUCs) were determined. RPD were present in 262 cases (no AMD, n = 9 [0.7%; early/intermediate AMD, n = 75 [12.4%]; late AMD, n = 178 [23.8%]). ROC analysis of the genetic model including age, rs2075650, rs10490924, rs800292, rs12144939, rs10033900, rs13081855, rs3812111, rs2049622, and rs4296082 revealed an AUC of 0.871. Considering all possible predictors, backward selection revealed a slightly different set of genetic factors, as well as the following nongenetic risk factors: smoking, rheumatoid arthritis, steroids, antiglaucomatous drugs, and past sunlight exposure; the results showed an AUC of 0.886. RPD share a variety of genetic and nongenetic risk factors with AMD. Future AMD grading systems should integrate RPD as an important risk phenotype.