June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Association of genetic risk of age-related macular degeneration with disease stages and endophenotypes
Author Affiliations & Notes
  • Davide Garzone
    Ophthalmology, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany
    Population Health Sciences, DZNE, German center for neurodegenerative diseases, Bonn, Germany
  • Mohammed Aslam Imtiaz
    Population Health Sciences, DZNE, German center for neurodegenerative diseases, Bonn, Germany
  • Matthias Marten Mauschitz
    Population Health Sciences, DZNE, German center for neurodegenerative diseases, Bonn, Germany
    Ophthalmology, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany
  • N Ahmad Aziz
    Population Health Sciences, DZNE, German center for neurodegenerative diseases, Bonn, Germany
  • Frank G Holz
    Ophthalmology, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany
  • Monique MB Breteler
    Population Health Sciences, DZNE, German center for neurodegenerative diseases, Bonn, Germany
  • Robert Patrick Finger
    Ophthalmology, Universitatsklinikum Bonn, Bonn, Nordrhein-Westfalen, Germany
  • Footnotes
    Commercial Relationships   Davide Garzone None; Mohammed Aslam Imtiaz None; Matthias Marten Mauschitz None; N Ahmad Aziz None; Frank Holz Acucela, Apellis, Bayer, Boehringer-Ingelheim, Bioeq/Formycon, Roche/Genentech, Geuder, Graybug, Gyroscope, Heidelberg Engineering, IvericBio, Kanghong, LinBioscience, Novartis, Oxurion, Pixium Vision, Oxurion, Stealth BioTherapeutics, Zeiss, Code C (Consultant/Contractor), Acucela, Allergan, Apellis, Bayer, Bioeq/Formycon, CenterVue, Ellex, Roche/Genentech, Geuder, Heidelberg Engineering, IvericBio, Kanghong, NightStarX, Novartis, Optos, Pixium Vision, Zeiss, Code F (Financial Support), GRADE Reading Center, Code O (Owner); Monique Breteler None; Robert Finger Bayer, Novartis , Roche/Genentech , Allergan, Alimera, Böhringer-Ingelheim, Santhera, Ellex, ProQR , Opthea, Oxford Innovation, Code C (Consultant/Contractor), Novartis, Zeiss, Heidelberg Engineering, CentreVue, Biogen, Code F (Financial Support)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1742. doi:
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      Davide Garzone, Mohammed Aslam Imtiaz, Matthias Marten Mauschitz, N Ahmad Aziz, Frank G Holz, Monique MB Breteler, Robert Patrick Finger; Association of genetic risk of age-related macular degeneration with disease stages and endophenotypes. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1742.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Assessment of the genetic risk of age-related macular degeneration (AMD) has been limited to few cohorts independent of recent discovery genome-wide association studies (GWAS), which often did not include early AMD individuals. Thus, we assessed the relation between AMD genetic risk and AMD stages and endophenotypes (including large drusen area (LDA) and reticular pseudodrusen (RPD)) in an independent population-based study.

Methods : We included 2546 individuals older than 50 years from the Rhineland Study, a population-based study in Bonn, Germany. Genetic risk scores (GRS) and subscores (complement, extracellular matrix remodeling (ECM) and lipid) were constructed as described previously. AMD grading was based on color fundus photography; multimodal imaging was consulted for grading RPD and any disagreements among graders. Associations between GRS and subscores were assessed using multinomial log-linear models for AMD and binomial logistic regression for AMD endophenotypes (RPD, LDA) adjusted for age, sex and genetic principal components.

Results : GRS and complement subscores gradually increased, but did not fully overlap, with advancing AMD stages. The ECM subscore increased only in late AMD. Among individuals with early and iAMD, one SD increase in GRS was associated with 1.76 [1.30 – 2.40] higher odds of RPD and 1.87 [1.21 – 2.96] higher odds of LDA. RPD were also associated with both increasing ECM and complement subscores (odds ratio (OR) for ECM: 1.48 [1.05 – 2.10], OR for complement: 1.71 [1.28 – 2.30]).

Conclusions : AMD genetic risk increases with advancing AMD stage. However, the ECM subscore only increased in late AMD, hence its role as a marker of AMD progression needs to be explored in future studies. RPD and LDA might indicate higher genetic risk in early stages of AMD. The lower tail of GRS distribution between early, intermediate and late AMD did not overlap, possibly indicating no to very low risk for AMD progression in individuals with low genetic risk.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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