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Sci Rep. 2019 Apr 29;9(1):6611. doi: 10.1038/s41598-019-43144-3.

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

Author information

1
Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
2
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands.
3
Department of Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands.
4
Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen, The Netherlands.
5
Department of Ophthalmology, Queens University Belfast, Belfast, United Kingdom.
6
Centre for Public Health, Queen's University of Belfast, Belfast, United Kingdom.
7
Department of Ophthalmology, St. Franziskus Hospital, Münster, Germany.
8
Institute of Epidemiology and Social Medicine, Westfälische Wilhelms University, Münster, Germany.
9
Department of Ophthalmology, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands. Anneke.denHollander@radboudumc.nl.
10
Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud university medical center, Nijmegen, The Netherlands. Anneke.denHollander@radboudumc.nl.

Abstract

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, R2 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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