Evidence map›Paper›PMID 38438351›Full record

ArticleNature communications2024

QTL mapping of human retina DNA methylation identifies 87 gene-epigenome interactions in age-related macular degeneration.

Jayshree Advani, Puja A Mehta, Andrew R Hamel, Sudeep Mehrotra, Christina Kiel, Tobias Strunz, Ximena Corso-Díaz, Madeline Kwicklis, Freekje van Asten, Rinki Ratnapriya and 7 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
8.9field-weighted citation impact, top 1% of its field
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

40 citing papers in PubMed, 39 citations in OpenAlex.

  1. Article
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  15. Genome-Wide Association Study for Glucocorticoid-Induced Ocular Hypertension.medRxiv : the preprint server for health sciences · 2026
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 2 countries.

Jayshree AdvaniNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Puja A MehtaOcular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA.ORCID 0000-0003-3205-1163
Andrew R HamelOcular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA.ORCID 0000-0001-6420-9573
Sudeep MehrotraOcular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA.
Christina KielInstitute of Human Genetics, University of Regensburg, Regensburg, Germany.ORCID 0000-0003-3154-4847
Tobias StrunzInstitute of Human Genetics, University of Regensburg, Regensburg, Germany.
Ximena Corso-DíazNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Madeline KwicklisNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Freekje van AstenNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Rinki RatnapriyaNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
Emily Y ChewDivision of Epidemiology and Clinical Applications, Clinical Trials Branch, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0003-0999-9802
Dena G HernandezLaboratory of Neurogenetics, National Institute of Aging, National Institutes of Health, Bethesda, MD, USA.
Sandra R MontezumaDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA.
Deborah A FerringtonDepartment of Ophthalmology and Visual Neurosciences, University of Minnesota, Minneapolis, MN, USA.
Bernhard H F WeberInstitute of Human Genetics, University of Regensburg, Regensburg, Germany.ORCID 0000-0002-8808-7723
Ayellet V SegrèOcular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA. ayellet_segre@meei.harvard.edu.
Anand SwaroopNeurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, MD, USA. swaroopa@nei.nih.gov.ORCID 0000-0002-1975-1141
National Institutes of Health · USBroad Institute · USUniversity of Minnesota · USUniversity of Regensburg · DEUniversity Hospital Regensburg · DE

Funding

Regulation of retinal developmentZIAEY000450 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2009 to 2025
$71.0M
Mechanisms, modeling and therapies of retinal and macular neurodegenerationZIAEY000546 · NEI · NATIONAL EYE INSTITUTE · PI SWAROOP, ANAND · 2015 to 2025
$36.3M
P30 Core Grant for Vision ResearchP30EY014104 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Janey L Wiggs · 2002 to 2026
$15.1M
Uncovering novel biological processes and pathogenic mechanisms for glaucomaR01EY031424 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Ayellet Vered Segre · 2020 to 2026
$4.5M
Mitochondrial defects in the retinal pigment epithelium and the CFH risk allele for age-related macular degenerationR01EY028554 · NEI · UNIVERSITY OF MINNESOTA · PI DUTTON, JAMES R., FERRINGTON, DEBORAH ANN · 2018 to 2025
$4.5M
Intramural NIH HHS ZIA EY000450Intramural NIH HHS ZIA EY000546NEI NIH HHS P30 EY014104NEI NIH HHS R01 EY028554NEI NIH HHS R01 EY031424
6 · The paper itself

Abstract

DNA methylation provides a crucial epigenetic mark linking genetic variations to environmental influence. We have analyzed array-based DNA methylation profiles of 160 human retinas with co-measured RNA-seq and >8 million genetic variants, uncovering sites of genetic regulation in cis (37,453 methylation quantitative trait loci and 12,505 expression quantitative trait loci) and 13,747 DNA methylation loci affecting gene expression, with over one-third specific to the retina. Methylation and expression quantitative trait loci show non-random distribution and enrichment of biological processes related to synapse, mitochondria, and catabolism. Summary data-based Mendelian randomization and colocalization analyses identify 87 target genes where methylation and gene-expression changes likely mediate the genotype effect on age-related macular degeneration. Integrated pathway analysis reveals epigenetic regulation of immune response and metabolism including the glutathione pathway and glycolysis. Our study thus defines key roles of genetic variations driving methylation changes, prioritizes epigenetic control of gene expression, and suggests frameworks for regulation of macular degeneration pathology by genotype-environment interaction in retina.

Indexed as

DNA MethylationMacular DegenerationEpigenesis, GeneticEpigenomeHumansRetina

Identifiers

PMID38438351
PMCPMC10912779
OpenAlexW4392367266

What Socratic 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 Socratic graph.