Modelling the genetic risk in age-related macular degeneration.

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...

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Autores principales:	Felix Grassmann, Lars G Fritsche, Claudia N Keilhauer, Iris M Heid, Bernhard H F Weber
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/07c42911a25f453083a544453d2b42b8
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spelling	oai:doaj.org-article:07c42911a25f453083a544453d2b42b82021-11-18T07:16:55ZModelling the genetic risk in age-related macular degeneration.1932-620310.1371/journal.pone.0037979https://doaj.org/article/07c42911a25f453083a544453d2b42b82012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22666427/?tool=EBIhttps://doaj.org/toc/1932-6203Late-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.Felix GrassmannLars G FritscheClaudia N KeilhauerIris M HeidBernhard H F WeberPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e37979 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Felix Grassmann Lars G Fritsche Claudia N Keilhauer Iris M Heid Bernhard H F Weber Modelling the genetic risk in age-related macular degeneration.
description	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.
format	article
author	Felix Grassmann Lars G Fritsche Claudia N Keilhauer Iris M Heid Bernhard H F Weber
author_facet	Felix Grassmann Lars G Fritsche Claudia N Keilhauer Iris M Heid Bernhard H F Weber
author_sort	Felix Grassmann
title	Modelling the genetic risk in age-related macular degeneration.
title_short	Modelling the genetic risk in age-related macular degeneration.
title_full	Modelling the genetic risk in age-related macular degeneration.
title_fullStr	Modelling the genetic risk in age-related macular degeneration.
title_full_unstemmed	Modelling the genetic risk in age-related macular degeneration.
title_sort	modelling the genetic risk in age-related macular degeneration.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/07c42911a25f453083a544453d2b42b8
work_keys_str_mv	AT felixgrassmann modellingthegeneticriskinagerelatedmaculardegeneration AT larsgfritsche modellingthegeneticriskinagerelatedmaculardegeneration AT claudiankeilhauer modellingthegeneticriskinagerelatedmaculardegeneration AT irismheid modellingthegeneticriskinagerelatedmaculardegeneration AT bernhardhfweber modellingthegeneticriskinagerelatedmaculardegeneration
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Modelling the genetic risk in age-related macular degeneration.

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