TY  - JOUR
A1  - Grassmann, Felix
A1  - Fritsche, Lars G.
A1  - Keilhauer, Claudia N.
A1  - Heid, Iris M.
A1  - Weber, Bernhard H. F.
T1  - Modelling the Genetic Risk in Age-Related Macular Degeneration
JF  - PLoS One
N2  - Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69-2.05) than patients aged 75 and above (1.45, 95% CI: 1.36-1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11-1131.96) for individuals in the highest category (GRS 3.44-5.18, 0.5% of the general population) compared to subjects with the most common genetic background (GRS -0.05-1.70, 40.2% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available.
KW  - AMD
KW  - complement factor-H
KW  - grading system
KW  - United States
KW  - vitamin C
KW  - prevalence
KW  - variants
KW  - susceptibility
KW  - association
KW  - maculopathy
KW  - variant genotypes
KW  - genetic loci
KW  - macular degeneration
KW  - genetics of disease
KW  - eyes
KW  - cased-control studies
KW  - genotyping
KW  - human genetics
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131315
VL  - 7
IS  - 5
ER  -