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7th International Symposium on AMD: Age-related Macular Degeneration – Understanding Pathogenetic Mechanisms of Disease

20.09. - 21.09.2019, Baden-Baden

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Genetic Risk Score has added value over initial clinical grading stage in predicting disease progression in patients with non-advanced age-related macular degeneration – the Muenster Aging and Retina Study (MARS)

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  • Thomas J. Heesterbeek - Nijmegen/NL
  • E.K. de Jong - Nijmegen/NL; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen/NL
  • I.E. Acar - Nijmegen/NL; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen/NL
  • J.M.M. Groenewoud - Department of Health Evidence, Radboud University Medical Centre, Nijmegen/NL
  • B. Liefers - Nijmegen/NL; Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen/NL
  • C.I. Sánchez - Nijmegen/NL; Diagnostic Image Analysis Group, Radboud University Medical Center, Nijmegen/NL
  • T. Peto - Belfast/GB, Centre for Public Health, Queen's University of Belfast, Belfast/GB
  • C.B. Hoyng - Nijmegen/NL
  • D. Pauleikhoff - Münster/D
  • H.W. Hense - Institute of Epidemiology and Social Medicine, Westfälische Wilhelms University, Münster/D
  • A.I. den Hollander - Nijmegen/NL; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen/NL

7th International Symposium on AMD: Age-related Macular Degeneration - Understanding Pathogenetic Mechanisms of Disease. Baden-Baden, 20.-21.09.2019. Düsseldorf: German Medical Science GMS Publishing House; 2020. Doc19amd05

doi: 10.3205/19amd05, urn:nbn:de:0183-19amd054

Published: February 5, 2020

© 2020 Heesterbeek et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

Outline

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Background: 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 study, we investigated the association between the genetic risk score (GRS) and disease progression in patients with non-advanced AMD, and explored the added value of the GRS in addition to the drusen coverage at baseline.

Methods: A total of 177 patients with non-advanced (early or intermediate) AMD in the worst eye at baseline and a follow-up visit after 6.5 years were selected from the Muenster Aging and Retina Study (MARS). After DNA genotyping, 52 AMD-associated variants were extracted to generate a GRS. Fundus images were graded according to the Age-Related Eye Disease Study (AREDS) basic clinical classification scale, and the drusen coverage was quantified using a computer-aided detection system.

Results: 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 disease progression.

Conclusion: 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.