Evidence map›Paper›PMID 39896457›Full record

ArticlebioRxiv : the preprint server for biology2025

Pyruvate and Related Energetic Metabolites Modulate Resilience Against High Genetic Risk for Glaucoma.

Keva Li, Nicholas Tolman, Ayellet V Segrè, Kelsey V Stuart, Oana A Zeleznik, Neeru A Vallabh, Kuang Hu, Nazlee Zebardast, Akiko Hanyuda, Yoshihiko Raita and 10 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

5 · Who and what money

Authors and funding

20 authors.

Keva LiDepartment of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0001-5922-4955
Nicholas TolmanDepartment of Ophthalmology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.
Ayellet V SegrèDepartment of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02142, USA.ORCID 0000-0001-6806-5845
Kelsey V StuartNIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, and University College London Institute of Ophthalmology, London, EC1V 2PD, United Kingdom.
Oana A ZeleznikChanning Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Neeru A VallabhDepartment of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, L69 3BX, United Kingdom.
Kuang HuNIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, and University College London Institute of Ophthalmology, London, EC1V 2PD, United Kingdom.
Nazlee ZebardastDepartment of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02142, USA.ORCID 0000-0003-1763-9401
Akiko HanyudaDepartment of Ophthalmology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Yoshihiko RaitaOkinawa Kenritsu, Chubu Byoin, Uruma, Okinawa 904-2293, Japan.
Christa MontgomeryDepartment of Ophthalmology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.ORCID 0009-0004-2430-2772
Chi ZhangDepartment of Ophthalmology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.
Pirro G HysiDepartment of Ophthalmology, St Thomas' Hospital, King's College London, London, SE1 7EH, United Kingdom.
Ron DoDepartment of Genetics and Genomics Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-3144-3627
Anthony P KhawajaNIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust, and University College London Institute of Ophthalmology, London, EC1V 2PD, United Kingdom.ORCID 0000-0001-6802-8585
Janey L WiggsDepartment of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston, MA 02142, USA.
Jae H KangChanning Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.ORCID 0000-0003-4812-0557
Simon Wm JohnDepartment of Ophthalmology, Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.ORCID 0000-0002-4319-0356
Louis R PasqualeDepartment of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.ORCID 0000-0002-5835-3496
UK Biobank Eye and Vision Consortium

Funding

P30 Core Grant for Vision ResearchP30EY014104 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Ayellet Vered Segre · 2002 to 2026
$15.1M
Instrumentation, Fabrication, and Design CoreP30EY019007 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Xin Zhang · 2010 to 2026
$12.3M
Cell Death Pathways in Glaucomatous NeurodegenerationR01EY018606 · NEI · UNIVERSITY OF ROCHESTER · PI JOHN, SIMON W, LIBBY, RICHARD T · 2008 to 2023
$5.8M
Uncovering novel biological processes and pathogenic mechanisms for glaucomaR01EY031424 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Ayellet Vered Segre · 2020 to 2026
$4.5M
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
Towards an integrated map of causal connections for common, complex diseasesR35GM124836 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Ron Do · 2017 to 2026
$3.9M
Does VECAD at Schlemm canal cell-junctions determine IOP and glaucoma risk?R01EY032062 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI JOHN, SIMON W, KIZHATIL, KRISHNAKUMAR · 2021 to 2025
$3.5M
Multiomic Framework for GlaucomaR01EY036460 · NEI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI JAE H KANG, Louis Robert Pasquale · 2024 to 2026
$2.4M
Models, mechanisms and treatment of LMX1B-induced glaucomaR01EY032507 · NEI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI JOHN, SIMON W · 2021 to 2024
$2.3M
Glaucoma Risk Prediction Using Machine Learning Integration of Image-Based Phenotypes and Genetic AssociationsK23EY032634 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI ZEBARDAST, NAZLEE · 2021 to 2024
$1.0M
NEI NIH HHS K23 EY032634NEI NIH HHS P30 EY014104NEI NIH HHS P30 EY019007NEI NIH HHS R01 EY018606NEI NIH HHS R01 EY031424NEI NIH HHS R01 EY032062NEI NIH HHS R01 EY032507NEI NIH HHS R01 EY032559NEI NIH HHS R01 EY036460NIGMS NIH HHS R35 GM124836
6 · The paper itself

Abstract

A glaucoma polygenic risk score (PRS) can effectively identify disease risk, but some individuals with high PRS do not develop glaucoma. Factors contributing to this resilience remain unclear. Using 4,658 glaucoma cases and 113,040 controls in a cross-sectional study of the UK Biobank, we investigated whether plasma metabolites enhanced glaucoma prediction and if a metabolomic signature of resilience in high-genetic-risk individuals existed. Logistic regression models incorporating 168 NMR-based metabolites into PRS-based glaucoma assessments were developed, with multiple comparison corrections applied. While metabolites weakly predicted glaucoma (Area Under the Curve=0.579), they offered marginal prediction improvement in PRS-only-based models (P=0.004). We identified a metabolomic signature associated with resilience in the top glaucoma PRS decile, with elevated glycolysis-related metabolites-lactate (P=8.8E-12), pyruvate (P=1.9E-10), and citrate (P=0.02)-linked to reduced glaucoma prevalence. These metabolites combined significantly modified the PRS-glaucoma relationship (P

Indexed as

genetic risk scoregeneticsglaucomaglaucoma resilienceglycolysismetabolite risk scoremetabolitespyruvatetricarboxylic acid cycle

Identifiers

PMID39896457
PMCPMC11785086

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.