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@ARTICLE{Garzone:271698,
author = {Garzone, David and Imtiaz, Mohammed Aslam and Mauschitz,
Matthias M and Aziz, N. Ahmad and Holz, Frank G and
Breteler, Monique and Finger, Robert P},
title = {{A}ge-{R}elated {M}acular {D}egeneration and {I}ts
{G}enetic {R}isk: {A} {P}opulation-based {S}tudy.},
journal = {Current eye research},
volume = {50},
number = {1},
issn = {0271-3683},
address = {Abingdon},
publisher = {Taylor $\&$ Francis Group},
reportid = {DZNE-2024-01053},
pages = {82 - 86},
year = {2025},
abstract = {Specific genetic factors might serve as markers for risk
stratification of AMD progression, but their association
with key features of AMD has not been fully elucidated.
Thus, we investigated the association between overall and
pathway-specific genetic risk scores (GRS) and lead loci
(ARMS2, CFH) with AMD stages and features of high-risk
nonlate AMD, including reticular pseudodrusen (RPD) and
large drusen area (LDA).We performed a cross-sectional
analysis of data from the Rhineland Study, a
population-based study in Bonn, Germany. We included 4016
individuals aged 50 years and older of European descent. GRS
and pathway-specific subscores were constructed based on a
large genome-wide association study of AMD. Subscores were
generated based on gene-pathways associations (complement,
extracellular matrix remodeling (ECM) and lipid metabolism).
Associations were assessed using logistic and multinomial
regression.The mean age of participants was 63.36 years and
1813 $(45.1\%)$ were men. The GRS was positive in $48.1\%$
of individuals and increased, but did not fully overlap,
across AMD stages. Pathway-specific subscores increased
across AMD stages except for the ECM subscore, which only
showed a trend for increasing in late AMD. Increasing
overall GRS was associated with RPD and LDA (OR $[95\%CI]$
for RPD: 1.70 [1.33-2.15], for LDA: 1.64 [1.29-2.07]) among
individuals with AMD. Similarly, higher complement and ECM
subscores was associated with RPD, while for LDA, only an
association with complement subscore was observed.In a
population-based setting, we confirmed higher genetic risk
to be associated with more severe AMD and identified
associations with high-risk features of intermediate AMD.
Conjoint analyses suggested that high-risk features and late
AMD might be differentially associated with genetic
architecture in AMD, such as ECM remodeling. Incorporation
of genetic information such as GRSs might improve AMD risk
prediction strategies.},
keywords = {Humans / Male / Female / Cross-Sectional Studies / Middle
Aged / Macular Degeneration: genetics / Macular
Degeneration: epidemiology / Aged / Genetic Predisposition
to Disease / Genome-Wide Association Study / Risk Factors /
Germany: epidemiology / Complement Factor H: genetics /
Polymorphism, Single Nucleotide / Retinal Drusen: genetics /
Retinal Drusen: epidemiology / Proteins: genetics /
Population Surveillance / Disease Progression / AMD (Other)
/ PRS (Other) / RPD (Other) / genetics (Other) / retina
(Other)},
cin = {AG Breteler / AG Aziz},
ddc = {610},
cid = {I:(DE-2719)1012001 / I:(DE-2719)5000071},
pnm = {354 - Disease Prevention and Healthy Aging (POF4-354)},
pid = {G:(DE-HGF)POF4-354},
experiment = {EXP:(DE-2719)Rhineland Study-20190321},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39155542},
doi = {10.1080/02713683.2024.2388692},
url = {https://pub.dzne.de/record/271698},
}