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Genetic risk score has added value over initial clinical grading stage in predicting disease progression in age-related macular degeneration

Several prediction models for progression of age-related macular degeneration (AMD) have been developed, but the added value of using genetic information in those models in addition to clinical characteristics is ambiguous. In this prospective cohort study, we explored the added value of genetics us...

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Autores principales: Heesterbeek, Thomas J., de Jong, Eiko K., Acar, Ilhan E., Groenewoud, Joannes M. M., Liefers, Bart, Sánchez, Clara I., Peto, Tunde, Hoyng, Carel B., Pauleikhoff, Daniel, Hense, Hans W., den Hollander, Anneke I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488669/
https://www.ncbi.nlm.nih.gov/pubmed/31036867
http://dx.doi.org/10.1038/s41598-019-43144-3
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author Heesterbeek, Thomas J.
de Jong, Eiko K.
Acar, Ilhan E.
Groenewoud, Joannes M. M.
Liefers, Bart
Sánchez, Clara I.
Peto, Tunde
Hoyng, Carel B.
Pauleikhoff, Daniel
Hense, Hans W.
den Hollander, Anneke I.
author_facet Heesterbeek, Thomas J.
de Jong, Eiko K.
Acar, Ilhan E.
Groenewoud, Joannes M. M.
Liefers, Bart
Sánchez, Clara I.
Peto, Tunde
Hoyng, Carel B.
Pauleikhoff, Daniel
Hense, Hans W.
den Hollander, Anneke I.
author_sort Heesterbeek, Thomas J.
collection PubMed
description Several prediction models for progression of age-related macular degeneration (AMD) have been developed, but the added value of using genetic information in those models in addition to clinical characteristics is ambiguous. In this prospective cohort study, we explored the added value of genetics using a genetic risk score (GRS) based on 52 AMD-associated variants, in addition to the clinical severity grading at baseline as quantified by validated drusen detection software, to predict disease progression in 177 AMD patients after 6.5 years follow-up. The GRS was strongly associated with the drusen coverage at baseline (P < 0.001) and both the GRS and drusen coverage were associated with disease progression. When the GRS was added as predictor in addition to the drusen coverage, R(2) increased from 0.46 to 0.56. This improvement by the GRS was predominantly seen in patients with a drusen coverage <15%. In patients with a larger drusen coverage, the GRS had less added value to predict progression. Thus, genetic information has added value over clinical characteristics in predicting disease progression in AMD, but only in patients with a less severe disease stage. Patients with a high GRS should be made aware of their risk and could be selected for clinical trials for arresting progression.
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spelling pubmed-64886692019-05-16 Genetic risk score has added value over initial clinical grading stage in predicting disease progression in age-related macular degeneration Heesterbeek, Thomas J. de Jong, Eiko K. Acar, Ilhan E. Groenewoud, Joannes M. M. Liefers, Bart Sánchez, Clara I. Peto, Tunde Hoyng, Carel B. Pauleikhoff, Daniel Hense, Hans W. den Hollander, Anneke I. Sci Rep Article Several prediction models for progression of age-related macular degeneration (AMD) have been developed, but the added value of using genetic information in those models in addition to clinical characteristics is ambiguous. In this prospective cohort study, we explored the added value of genetics using a genetic risk score (GRS) based on 52 AMD-associated variants, in addition to the clinical severity grading at baseline as quantified by validated drusen detection software, to predict disease progression in 177 AMD patients after 6.5 years follow-up. The GRS was strongly associated with the drusen coverage at baseline (P < 0.001) and both the GRS and drusen coverage were associated with disease progression. When the GRS was added as predictor in addition to the drusen coverage, R(2) increased from 0.46 to 0.56. This improvement by the GRS was predominantly seen in patients with a drusen coverage <15%. In patients with a larger drusen coverage, the GRS had less added value to predict progression. Thus, genetic information has added value over clinical characteristics in predicting disease progression in AMD, but only in patients with a less severe disease stage. Patients with a high GRS should be made aware of their risk and could be selected for clinical trials for arresting progression. Nature Publishing Group UK 2019-04-29 /pmc/articles/PMC6488669/ /pubmed/31036867 http://dx.doi.org/10.1038/s41598-019-43144-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Heesterbeek, Thomas J.
de Jong, Eiko K.
Acar, Ilhan E.
Groenewoud, Joannes M. M.
Liefers, Bart
Sánchez, Clara I.
Peto, Tunde
Hoyng, Carel B.
Pauleikhoff, Daniel
Hense, Hans W.
den Hollander, Anneke I.
Genetic risk score has added value over initial clinical grading stage in predicting disease progression in age-related macular degeneration
title Genetic risk score has added value over initial clinical grading stage in predicting disease progression in age-related macular degeneration
title_full Genetic risk score has added value over initial clinical grading stage in predicting disease progression in age-related macular degeneration
title_fullStr Genetic risk score has added value over initial clinical grading stage in predicting disease progression in age-related macular degeneration
title_full_unstemmed Genetic risk score has added value over initial clinical grading stage in predicting disease progression in age-related macular degeneration
title_short Genetic risk score has added value over initial clinical grading stage in predicting disease progression in age-related macular degeneration
title_sort genetic risk score has added value over initial clinical grading stage in predicting disease progression in age-related macular degeneration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488669/
https://www.ncbi.nlm.nih.gov/pubmed/31036867
http://dx.doi.org/10.1038/s41598-019-43144-3
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