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Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages

BACKGROUND: Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic factor...

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Autores principales: Schick, Tina, Altay, Lebriz, Viehweger, Eva, Hoyng, Carel B., den Hollander, Anneke I., Felsch, Moritz, Fauser, Sascha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892556/
https://www.ncbi.nlm.nih.gov/pubmed/27257685
http://dx.doi.org/10.1371/journal.pone.0156778
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author Schick, Tina
Altay, Lebriz
Viehweger, Eva
Hoyng, Carel B.
den Hollander, Anneke I.
Felsch, Moritz
Fauser, Sascha
author_facet Schick, Tina
Altay, Lebriz
Viehweger, Eva
Hoyng, Carel B.
den Hollander, Anneke I.
Felsch, Moritz
Fauser, Sascha
author_sort Schick, Tina
collection PubMed
description BACKGROUND: Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic factors and different AMD stages depending on unilateral and bilateral disease severity. METHODS: In this case-control study, participants were assigned to nine AMD severity stages based on the characteristics of each eye. 18 single nucleotide polymorphisms (SNPs) were genotyped and attempted to correlate with AMD severity stages by uni- and multivariate logistic regression analyses and trend analyses. Area under the receiver operating characteristic curves (AUC) were calculated. RESULTS: Of 3444 individuals 1673 were controls, 379 had early AMD, 333 had intermediate AMD and 989 showed late AMD stages. With increasing severity of disease and bilateralism more SNPs with significant associations were found. Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71). Trend analyses showed p<0.0001 for ARMS2 (rs10490924) and for CFH (rs1061170), respectively. AUC of risk models for various AMD severity stages was lowest for unilateral early AMD (AUC = 0.629) and showed higher values in more severely and bilaterally affected individuals being highest for late AMD with GA in one eye and neovascular AMD in the other eye (AUC = 0.957). CONCLUSION: The association of known genetic risk factors with AMD became stronger with increasing disease severity, which also led to an increasing discriminative ability of AMD cases and controls. Genetic predisposition was also associated with the disease severity of the fellow-eye, highlighting the importance of both eyes in AMD patients.
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spelling pubmed-48925562016-06-16 Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages Schick, Tina Altay, Lebriz Viehweger, Eva Hoyng, Carel B. den Hollander, Anneke I. Felsch, Moritz Fauser, Sascha PLoS One Research Article BACKGROUND: Age-related macular degeneration (AMD) is a common disease causing visual impairment and blindness. Various gene variants are strongly associated with late stage AMD, but little is known about the genetics of early forms of the disease. This study evaluated associations of genetic factors and different AMD stages depending on unilateral and bilateral disease severity. METHODS: In this case-control study, participants were assigned to nine AMD severity stages based on the characteristics of each eye. 18 single nucleotide polymorphisms (SNPs) were genotyped and attempted to correlate with AMD severity stages by uni- and multivariate logistic regression analyses and trend analyses. Area under the receiver operating characteristic curves (AUC) were calculated. RESULTS: Of 3444 individuals 1673 were controls, 379 had early AMD, 333 had intermediate AMD and 989 showed late AMD stages. With increasing severity of disease and bilateralism more SNPs with significant associations were found. Odds ratios, especially for the main risk polymorphisms in ARMS2 (rs10490924) and CFH (rs1061170), gained with increasing disease severity and bilateralism (exemplarily: rs1061170: unilateral early AMD: OR = 1.18; bilateral early AMD: OR = 1.20; unilateral intermediate AMD: OR = 1.28; bilateral intermediate AMD: OR = 1.39, unilateral geographic atrophy (GA): OR = 1.50; bilateral GA: OR = 1.71). Trend analyses showed p<0.0001 for ARMS2 (rs10490924) and for CFH (rs1061170), respectively. AUC of risk models for various AMD severity stages was lowest for unilateral early AMD (AUC = 0.629) and showed higher values in more severely and bilaterally affected individuals being highest for late AMD with GA in one eye and neovascular AMD in the other eye (AUC = 0.957). CONCLUSION: The association of known genetic risk factors with AMD became stronger with increasing disease severity, which also led to an increasing discriminative ability of AMD cases and controls. Genetic predisposition was also associated with the disease severity of the fellow-eye, highlighting the importance of both eyes in AMD patients. Public Library of Science 2016-06-03 /pmc/articles/PMC4892556/ /pubmed/27257685 http://dx.doi.org/10.1371/journal.pone.0156778 Text en © 2016 Schick et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Schick, Tina
Altay, Lebriz
Viehweger, Eva
Hoyng, Carel B.
den Hollander, Anneke I.
Felsch, Moritz
Fauser, Sascha
Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages
title Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages
title_full Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages
title_fullStr Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages
title_full_unstemmed Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages
title_short Genetics of Unilateral and Bilateral Age-Related Macular Degeneration Severity Stages
title_sort genetics of unilateral and bilateral age-related macular degeneration severity stages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4892556/
https://www.ncbi.nlm.nih.gov/pubmed/27257685
http://dx.doi.org/10.1371/journal.pone.0156778
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