Evidence map›Paper›PMID 34743558›Full record

ArticleCirculation2022

Deep Learning of the Retina Enables Phenome- and Genome-Wide Analyses of the Microvasculature.

Seyedeh Maryam Zekavat, Vineet K Raghu, Mark Trinder, Yixuan Ye, Satoshi Koyama, Michael C Honigberg, Zhi Yu, Akhil Pampana, Sarah Urbut, Sara Haidermota and 12 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
106citing papers in PubMed, 1 pooled it
15.0field-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

106 citing papers in PubMed, 1 synthesis or guideline pooled it, 164 citations in OpenAlex.

  1. Pooled it
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  7. Mendelian randomization evidence refines retinal alterations in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  12. Genetic analysis of imaging-derived phenotypes.Nature reviews. Genetics · 2026
    Review
  13. Retinal imaging for cerebrovascular risk stratification: evidence, limitations, and practical thresholds for the ophthalmologist.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2026
    Review
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46 more citing papers are in PubMed but not listed here.

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

22 authors at 6 institutions in 3 countries.

Seyedeh Maryam Zekavat *Department of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, CT (S.M.Z., J.M., R.A.A., L.D.P., J.C.W.).ORCID 0000-0003-4026-8944
Vineet K Raghu *Program in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., V.K.R., M.T., S.K., M.C.H., Z.Y., A.P., S.U., P.T.E., P.N.).ORCID 0000-0003-3524-3945
Mark TrinderCentre for Heart Lung Innovation, University of British Columbia, Vancouver, Canada (M.T.).
Yixuan YeComputational Biology & Bioinformatics Program (S.M.Z., Y.Y., H.Z.), Yale University, New Haven, CT.ORCID 0000-0002-2643-665X
Satoshi KoyamaProgram in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., V.K.R., M.T., S.K., M.C.H., Z.Y., A.P., S.U., P.T.E., P.N.).
Michael C HonigbergProgram in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., V.K.R., M.T., S.K., M.C.H., Z.Y., A.P., S.U., P.T.E., P.N.).ORCID 0000-0001-8630-5021
Zhi YuProgram in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., V.K.R., M.T., S.K., M.C.H., Z.Y., A.P., S.U., P.T.E., P.N.).ORCID 0000-0003-4810-3474
Akhil PampanaProgram in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., V.K.R., M.T., S.K., M.C.H., Z.Y., A.P., S.U., P.T.E., P.N.).ORCID 0000-0002-4167-0540
Sarah UrbutProgram in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., V.K.R., M.T., S.K., M.C.H., Z.Y., A.P., S.U., P.T.E., P.N.).ORCID 0000-0002-1135-9647
Sara HaidermotaCardiovascular Research Center (S.M.Z., V.K.R., M.C.H., S.U., S.H., P.T.E., P.N.), Massachusetts General Hospital, Harvard Medical School, Boston.
Declan P O'ReganMRC London Institute of Medical Sciences, Imperial College London, UK (D.P.O.).
Hongyu ZhaoComputational Biology & Bioinformatics Program (S.M.Z., Y.Y., H.Z.), Yale University, New Haven, CT.ORCID 0000-0003-1195-9607
Patrick T EllinorProgram in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., V.K.R., M.T., S.K., M.C.H., Z.Y., A.P., S.U., P.T.E., P.N.).ORCID 0000-0002-2067-0533
Ayellet V SegrèDepartment of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston (A.V.S., T.E., J.L.W., N.Z.).
Tobias ElzeDepartment of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston (A.V.S., T.E., J.L.W., N.Z.).ORCID 0000-0002-2032-0496
Janey L WiggsDepartment of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston (A.V.S., T.E., J.L.W., N.Z.).ORCID 0000-0003-1890-3278
James MartoneDepartment of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, CT (S.M.Z., J.M., R.A.A., L.D.P., J.C.W.).
Ron A AdelmanDepartment of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, CT (S.M.Z., J.M., R.A.A., L.D.P., J.C.W.).
Nazlee ZebardastDepartment of Ophthalmology, Massachusetts Eye and Ear, Harvard Medical School, Boston (A.V.S., T.E., J.L.W., N.Z.).
Lucian Del PrioreDepartment of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, CT (S.M.Z., J.M., R.A.A., L.D.P., J.C.W.).
Jay C WangDepartment of Ophthalmology and Visual Science, Yale School of Medicine, New Haven, CT (S.M.Z., J.M., R.A.A., L.D.P., J.C.W.).
Pradeep NatarajanProgram in Medical and Population Genetics and Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA (S.M.Z., V.K.R., M.T., S.K., M.C.H., Z.Y., A.P., S.U., P.T.E., P.N.).ORCID 0000-0001-8402-7435
Broad Institute · USYale University · USMassachusetts Eye and Ear Infirmary · USLung Institute · USMassachusetts General Hospital · USMRC London Institute of Medical Sciences · GB

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Using genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3M
Clonal hematopoiesis in humans: determinants of development and progressionR01HL148050 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI BALLANTYNE, CHRISTIE MITCHELL, NATARAJAN, PRADEEP · 2019 to 2022
$5.9M
Whole genome sequences in individuals to comprehensively characterize the genetic mechanisms of dyslipidemiasR01HL142711 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Satoshi Koyama, Gina Marie Peloso · 2019 to 2026
$4.7M
Clonal hematopoiesis of indeterminate potential and HIV in the REPRIEVE trialR01HL151283 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI NATARAJAN, PRADEEP · 2020 to 2023
$2.5M
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
British Heart Foundation NH/17/1/32725British Heart Foundation RE/18/4/34215British Heart Foundation RG/19/6/34387Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MC_UP_1605/13NCATS NIH HHS UL1 TR001863NEI NIH HHS K23 EY032634NHLBI NIH HHS R01 HL127564NHLBI NIH HHS R01 HL142711NHLBI NIH HHS R01 HL148050NHLBI NIH HHS R01 HL151283
6 · The paper itself

Abstract

backgroundThe microvasculature, the smallest blood vessels in the body, has key roles in maintenance of organ health and tumorigenesis. The retinal fundus is a window for human in vivo noninvasive assessment of the microvasculature. Large-scale complementary machine learning-based assessment of the retinal vasculature with phenome-wide and genome-wide analyses may yield new insights into human health and disease.

methodsWe used 97 895 retinal fundus images from 54 813 UK Biobank participants. Using convolutional neural networks to segment the retinal microvasculature, we calculated vascular density and fractal dimension as a measure of vascular branching complexity. We associated these indices with 1866 incident

resultsLow retinal vascular fractal dimension and density were significantly associated with higher risks for incident mortality, hypertension, congestive heart failure, renal failure, type 2 diabetes, sleep apnea, anemia, and multiple ocular conditions, as well as corresponding quantitative traits. Genome-wide association of vascular fractal dimension and density identified 7 and 13 novel loci, respectively, that were enriched for pathways linked to angiogenesis (eg, vascular endothelial growth factor, platelet-derived growth factor receptor, angiopoietin, and WNT signaling pathways) and inflammation (eg, interleukin, cytokine signaling).

conclusionsOur results indicate that the retinal vasculature may serve as a biomarker for future cardiometabolic and ocular disease and provide insights into genes and biological pathways influencing microvascular indices. Moreover, such a framework highlights how deep learning of images can quantify an interpretable phenotype for integration with electronic health record, biomarker, and genetic data to inform risk prediction and risk modification.

Indexed as

Deep LearningFemaleGenome-Wide Association StudyGenomicsHumansMaleMendelian Randomization AnalysisMicrovesselsMiddle AgedRetinadeep learningepidemiologygenomicsmendelian randomization analysismicrovesselsretina

Identifiers

PMID34743558
PMCPMC8746912
OpenAlexW3212362219

What OpenQuestion holds

Textmetadata
LicenceTDM
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.