Evidence map›Paper›PMID 41002105›Full record

ArticleTranslational vision science & technology2025

Associations Between Structural Phenotype and Polygenic Risk Scores in Intermediate Age-Related Macular Degeneration - A MACUSTAR Report.

Lukas Schloesser, Jan H Terheyden, Charlotte Behning, Hannah Klinkhammer, Davide Garzone, Marlene Saßmannshausen, Sarah Thiele, Steffen Schmitz-Valckenberg, Carel Hoyng, Clara I Sánchez and 7 more

Abstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Translational vision science & technology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Lukas SchloesserDepartment of Ophthalmology, University of Bonn, Bonn, Germany.
Jan H TerheydenDepartment of Ophthalmology, University of Bonn, Bonn, Germany.
Charlotte BehningDepartment of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
Hannah KlinkhammerInstitute for Medical Biometry and Statistics, Medical Faculty, Phillips-University Marburg, Marburg, Germany.
Davide GarzoneDepartment of Ophthalmology, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Marlene SaßmannshausenDepartment of Ophthalmology, University of Bonn, Bonn, Germany.
Sarah ThieleDepartment of Ophthalmology, University of Bonn, Bonn, Germany.
Steffen Schmitz-ValckenbergDepartment of Ophthalmology, University of Bonn, Bonn, Germany.
Carel HoyngRUMC Nijmegen, Nijmegen, The Netherlands.
Clara I SánchezInformatics Institute, University of Amsterdam, Amsterdam, The Netherlands.
Matthias SchmidDepartment of Medical Biometry, Informatics and Epidemiology, University of Bonn, Bonn, Germany.
Ulrich F O LuhmannRoche Pharmaceutical Research and Early Development, Translational Medicine Ophthalmology, Roche Innovation Center, Basel, Switzerland.
Heather FloydNovartis Pharma AG, Basel, Switzerland.
Sergio LealBayer Consumer Care AG, Basel, Switzerland.
Frank G HolzDepartment of Ophthalmology, University of Bonn, Bonn, Germany.
Robert P FingerDepartment of Ophthalmology, University of Bonn, Bonn, Germany.
MACUSTAR Consortium

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Purpose: The purpose of this study was to analyze genotype-phenotype associations in intermediate age-related macular degeneration (iAMD) based on global and pathway-specific polygenic risk scores (psPRS) in participants of the prospective European multicenter cohort study MACUSTAR. Methods: Assessed structural biomarkers included reticular pseudodrusen (RPD), pigmentary abnormalities, hyper-reflective foci (HRF), and incomplete or complete retinal pigment epithelium (RPE) and outer retinal atrophy (iRORA and cRORA). Blood samples were genotyped and imputed via a local pipeline. Global and pathway-specific PRS (complement PRS [C-PRS], with and without ARMS2/HTRA1 variants [C+AH-PRS and AH-PRS]; extracellular matrix PRS [E-PRS]; and lipid PRS [L-PRS]) were calculated. The associations between global and pathway-specific PRS and structural iAMD biomarkers were assessed with multivariable models, controlling for age and sex. Results: In total, 404 participants (263 women, 65.1%; mean age = 71.5 ± 7.0 years, mean ± standard deviation [SD]) were included in the analysis. Multivariable regression models revealed that RPD was associated with a higher AH-PRS (estimate = 7.11 × 10-2, P = 9.0 × 10-3), C+AH-PRS (estimate = 9.96 × 10-2, P = 5.0 × 10-3), and E-PRS (estimate = 3.28 × 10-2, P = 3.1 × 10-2). The presence of cRORA was associated with a higher AH-PRS (estimate = 1.34 × 10-1, P = 2 × 10-3) and a higher C+AH-PRS (estimate = 1.59 × 10-1, P = 6 × 10-3). Conclusions: Structural risk biomarkers are associated with psPRS in iAMD. These findings further underscore the heterogeneity of pathogenic pathways in AMD and indicate differential risk characteristics across the broad spectrum of iAMD. Translational Relevance: Our findings reveal subgroups in iAMD based on genotype-phenotype associations which can help identifying patients at high risk for iAMD and establish new endpoints for clinical trials in iAMD.

Indexed as

Macular DegenerationMultifactorial InheritanceAgedAged, 80 and overBiomarkersFemaleGenetic Predisposition to DiseaseGenetic Risk ScoreHumansMaleMiddle AgedPhenotypeProspective StudiesProteinsRetinal Pigment EpitheliumRisk FactorsARMS2 protein, humanBiomarkersProteins

Identifiers

PMID41002105
PMCPMC12489858

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.