Evidence map›Paper›PMID 42818461›Full record

ArticlemedRxiv : the preprint server for health sciences2026

Genetic discovery using deep learning-derived optic nerve integrity phenotypes.

Asma M Aman, Eslam Zaher, Santiago Diaz-Torres, Sjoerd J Driessen, Victor A de Vries, Frank Ct van der Heide, Antonia Kolovos, Joshua M Schmidt, Henry N Marshall, Lania Saleh and 38 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

48 authors.

Asma M AmanQIMR Berghofer, Brisbane, Queensland, Australia.
Eslam ZaherQIMR Berghofer, Brisbane, Queensland, Australia.
Santiago Diaz-TorresQIMR Berghofer, Brisbane, Queensland, Australia.
Sjoerd J DriessenDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.
Victor A de VriesDepartment of Ophthalmology, Erasmus Medical Center, Rotterdam, Netherlands.
Frank Ct van der HeideCardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.
Antonia KolovosDepartment of Ophthalmology, Flinders University, Adelaide, Australia.
Joshua M SchmidtDepartment of Ophthalmology, Flinders University, Adelaide, Australia.
Henry N MarshallDepartment of Ophthalmology, Flinders University, Adelaide, Australia.
Lania SalehSection of Ophthalmology, King's College London, London, United Kingdom.
Alicia SchulzeInstitute of Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, Mainz, Germany.
Gabriëlla A BloklandDepartment of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, Netherlands.
Carroll A WebersUniversity Eye Clinic Maastricht, Maastricht University Medical Center +, Maastricht, Netherlands.
Carla J van der KallenCardiovascular Research Institute Maastricht, Maastricht University, Maastricht, Netherlands.
Anke WesseliusDepartment of Complex Genetics and Epidemiology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, Netherlands.
Ilja ArtsMaastricht Centre for Systems Biology, Maastricht University, Maastricht, Netherlands.
Freekje van AstenUniversity Eye Clinic Maastricht, Maastricht University Medical Center +, Maastricht, Netherlands.
Mathias GorskiDepartment of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Martina E ZimmermannDepartment of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Klaus J StarkDepartment of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Iris M HeidDepartment of Genetic Epidemiology, University of Regensburg, Regensburg, Germany.
Terri L YoungDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, United States.
Louis R PasqualeDepartment of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, United States.
Ayellet V SegrèDepartment of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, United States.
Janey L WiggsDepartment of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, Massachusetts, United States.
Anthony P KhawajaNIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom.
Donald J ZackJohns Hopkins University School of Medicine, Baltimore, United States.
Raymond C WongCentre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Australia.
Alex W HewittMenzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
Alexander K SchusterDepartment of Ophthalmology, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
Tos T BerendschotUniversity Eye Clinic Maastricht, Maastricht University Medical Center +, Maastricht, Netherlands.
Alberta A ThiadensDepartment of Ophthalmology, Erasmus Medical Center, Rotterdam, Netherlands.
Karin A van GarderenDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.
Caroline C W KlaverDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands.
Pirro G HysiSection of Ophthalmology, King's College London, London, United Kingdom.
Christopher J HammondSection of Ophthalmology, King's College London, London, United Kingdom.
Caroline BrandlDepartment of Ophthalmology, University Hospital Regensburg, Regensburg, Germany.
Jamie E CraigDepartment of Ophthalmology, Flinders University, Adelaide, Australia.
Wishal D RamdasDepartment of Ophthalmology, Erasmus Medical Center, Rotterdam, Netherlands.
Ya Xing WangBeijing Visual Science and Translational Eye Research Institute (BERI), Beijing Tsinghua Changgung Hospital, Tsinghua Medicine, Tsinghua University, Beijing, China.
Jost B JonasBeijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital University of Medical Science, Beijing, China.
Fred RoostaARC Training Centre for Information Resilience (CIRES), Brisbane, Queensland, Australia.
Michael L HunterBusselton Population Medical Research Foundation, Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Western Australia, Australia.
Stuart MacGregorQIMR Berghofer, Brisbane, Queensland, Australia.
Samantha S LeeCentre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, Perth, Western Australia, Australia.
David A MackeyMenzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
Maciej TrzaskowskiQIMR Berghofer, Brisbane, Queensland, Australia.
Puya GharahkhaniQIMR Berghofer, Brisbane, Queensland, Australia.

Funding

Understanding the clinical impact of cumulative genetic risk to glaucomaR01EY032559 · NEI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Louis Robert Pasquale, Janey L Wiggs · 2021 to 2026
$4.3M
Multiomic Framework for GlaucomaR01EY036460 · NEI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI JAE H KANG, Louis Robert Pasquale · 2024 to 2026
$2.4M
NEI NIH HHS R01 EY032559NEI NIH HHS R01 EY036460Wellcome Trust
6 · The paper itself

Abstract

The peripapillary retinal nerve fibre layer (pRNFL) thickness and Bruch's membrane opening-minimum rim width (BMO-MRW) are three-dimensional retinal biomarkers for glaucoma. We aimed to demonstrate that AI-derived thickness from two-dimensional fundus images can act as proxies, enabling the discovery of novel neurodegenerative loci. AI-derived pRNFL and BMO-MRW strongly correlated with OCT-derived thickness (r: 0.69 and 0.79, respectively). After validation, these phenotypes were predicted in two cohorts lacking disc-centred OCT: the UK Biobank and the Canadian Longitudinal Study on Aging. The predicted phenotypes showed strong genetic correlations with directly measured phenotypes from a previous study for both phenotypes (0.70 and 0.96, respectively). This data increased statistical power, identifying 29 loci for pRNFL thickness and 122 loci for BMO-MRW, including 14 loci that were independent of VCDR. We observed shared and sector-specific thickness loci overlapping glaucoma loci and revealed loci independent of known risk factors. Together, these results emphasise that multidimensional inferences can be drawn from 2D imaging, enabling downstream genetic analyses.

Indexed as

Bruch’s membrane opening-minimum rim widthCLSADeep learningfundus imagesglaucomaperipapillary retinal nerve fibre layer thicknessUK Biobank

Identifiers

PMID42818461
PMCPMC13622767

What OpenQuestion holds

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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.