Modelling the Genetic Risk in Age-Related Macular Degeneration
Please always quote using this URN: urn:nbn:de:bvb:20-opus-131315
- 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,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.…
Author: | Felix Grassmann, Lars G. Fritsche, Claudia N. Keilhauer, Iris M. Heid, Bernhard H. F. Weber |
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URN: | urn:nbn:de:bvb:20-opus-131315 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Augenklinik und Poliklinik |
Language: | English |
Parent Title (English): | PLoS One |
Year of Completion: | 2012 |
Volume: | 7 |
Issue: | 5 |
Pagenumber: | e37979 |
Source: | PLoS ONE 7(5): e37979. doi:10.1371/journal.pone.0037979 |
DOI: | https://doi.org/10.1371/journal.pone.0037979 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | AMD; United States; association; cased-control studies; complement factor-H; eyes; genetic loci; genetics of disease; genotyping; grading system; human genetics; macular degeneration; maculopathy; prevalence; susceptibility; variant genotypes; variants; vitamin C |
Release Date: | 2016/12/13 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung |