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Eric F. Thee, Johanna Colijn, Magda A. Meester, Anneke Den Hollander, Timo Verzijden, Caroline Klaver; The phenotype of the ARMS2 risk variant in age-related macular degeneration. Findings from the E3 & EYE-RISK consortium. Invest. Ophthalmol. Vis. Sci. 2020;61(7):2312.
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© ARVO (1962-2015); The Authors (2016-present)
To explore the phenotype of the genetic risk variant in ARMS2 rs3750846 in age-related macular degeneration (AMD). We determined prevalence and phenotypic profile of early, intermediate and late AMD phenotypes per ARMS2 genotype in the large E3/EYE-RISK consortium.
A total of 17,204 participants aged 69.3 years (SD 10.1) from 4 European population-based studies and 3 case control studies with ARMS2 genotype and AMD phenotype (rs3750846) were available for analyses. AMD lesions were graded by multimodal imaging (color fundus photos and OCT), and included presence of geographic atrophy (GA), choroidal neovascularization (CNV), mixed late AMD phenotype, drusen size, drusen area ≥10% within the ETDRS grid, presence of reticular pseudodrusen, hyperpigmentation, RPE-degeneration, as well as disease severity according to well-known AMD classification systems. Prevalence analyses were performed on population-based studies; risk analyses were performed on the entire cohort using regression analysis with adjustments for age, sex and multiple testing.
Prevalence of late AMD varied per ARMS2 status, and ranged from 2.1% for those with no risk alleles (n = 177), 4.3% for those with one risk allele (n = 183) and 9.7% for those with two risk alleles (n = 49). For those with two risk alleles of the variant, the odds ratio (OR) for late AMD was 10.7 (95% confidence interval [CI], 9.2 – 12.4), for GA 8.7 (95% CI 6.6 – 11.5) for CNV 10.7 (95% CI 9.0 – 12.8) and for mixed late AMD phenotype 13.8 (95% CI 9.7 – 19.6). Presence of two risk alleles was associated with reticular pseudodrusen (OR 5.3, 95% CI 2.8 – 9.6]), drusen area ≥10% (OR 4.8, 95% CI: 3.4 – 6.9), large drusen (OR 2.1, 95% CI: 1.2 – 2.1), hyperpigmentation (OR 1.6, 95% CI: 1.3 – 2.0) and RPE degeneration (OR 1.5, 95% CI: 1.2 – 1.9), but not significantly associated with small or intermediate sized drusen.
This study confirms earlier observations that the ARMS2 variant particularly predisposes to reticular drusen, large drusen area, and neovascular AMD phenotypes. ARMS2 appears to be acting most prominently in the later stages of the disease process. This makes this gene particularly interesting as a target for intervention research.
This is a 2020 ARVO Annual Meeting abstract.
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