Evidence map›Paper›PMID 34166655›Full record

SynthesisAmerican journal of ophthalmology2022

Gene Set Enrichment Analsyes Identify Pathways Involved in Genetic Risk for Diabetic Retinopathy.

Lucia Sobrin, Gayatri Susarla, Lynn Stanwyck, John M Rouhana, Ashley Li, Samuela Pollack, Robert P Igo, Richard A Jensen, Xiaohui Li, Maggie C Y Ng and 20 more

Erratum issuedOpen access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in American journal of ophthalmology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
2.2field-weighted citation impact, top 12% 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

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Precision Medicine in Type 1 Diabetes.Journal of the Indian Institute of Science · 2023
    Review
  6. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 17 institutions in 4 countries.

Lucia SobrinFrom the Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary. Electronic address: lucia_sobrin@meei.harvard.edu.
Gayatri SusarlaFrom the Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary.
Lynn StanwyckFrom the Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary.
John M RouhanaFrom the Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary.
Ashley LiFrom the Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary.
Samuela PollackDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Robert P IgoDepartment of Population and Quantitative Health Sciences, Case Western University, Cleveland, Ohio.
Richard A JensenCardiovascular Health Research Unit, Department of Medicine, Epidemiology and Health Services, University of Washington, Seattle, Washington.
Xiaohui LiInstitute for Translational Genomics and Population Sciences, Department of Pediatrics, the Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California.
Maggie C Y NgCenter for Genomics and Personalized Medicine Research, Wake Forest School of Medicine; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; Vanderbilt Genetics Institute and Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Albert V SmithDepartment of Medicine, University of Iceland, Reykjavík, Iceland.
Jane Z KuoMedical Affairs, Ophthalmology, Sun Pharmaceutical Industries, Inc, Princeton, New Jersey.
Kent D TaylorInstitute for Translational Genomics and Population Sciences, Department of Pediatrics, the Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California.
Barry I FreedmanCenter for Genomics and Personalized Medicine Research, Wake Forest School of Medicine; Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina.
Donald W BowdenCenter for Genomics and Personalized Medicine Research, Wake Forest School of Medicine; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Alan PenmanDepartment of Preventive Medicine, John D. Bower School of Population Health (A.P.), Department of Ophthalmology.
Ching J ChenDepartment of Preventive Medicine, John D. Bower School of Population Health (A.P.), Department of Ophthalmology.
Jamie E CraigUniversity of Mississippi Medical Center, Jackson, Mississippi, USA, FHMRI Eye & Vision, Flinders University, Bedford Park, SA, Australia.
Sharon G AdlerDepartment of Nephrology and Hypertension, Los Angeles Biomedical Research Institute at Harbor-University of California, Torrance, California.
Emily Y ChewDivision of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Mary Frances CotchDivision of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, Maryland.
Brian YaspanGenentech Inc, South San Francisco, California, USA.
Paul MitchellDepartment of Ophthalmology, Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia.
Jie Jin WangDepartment of Ophthalmology, Centre for Vision Research, Westmead Institute for Medical Research, University of Sydney, Sydney, Australia; Center of Clinician-Scientist Development, Duke-NUS Medical School, Singapore.
Barbara E K KleinDepartment of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Tien Y WongCenter of Clinician-Scientist Development, Duke-NUS Medical School, Singapore; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Department of Pediatrics, the Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California.
Kathyrn P BurdonMenzies Institute for Medical Research, University of Tasmania, Hobart, Australia.
Sudha K IyengarDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Population and Quantitative Health Sciences, Case Western University, Cleveland, Ohio.
Ayellet V SegrèFrom the Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary; Broad Institute of Harvard and MIT, Cambridge, Massachusetts.
Massachusetts Eye and Ear Infirmary · USUCLA Medical Center · USWake Forest University · USHarvard University · USNational Institutes of Health · USThe University of Sydney · AUWolters Kluwer Health · USBroad Institute · USFlinders University · AUSingapore National Eye Center · SGSun Pharma (United States) · USThe Lundquist Institute · USUniversity of Iceland · ISUniversity of Tasmania · AUUniversity of Washington · USUniversity of Wisconsin–Madison · USWestern University of Health Sciences · US

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
ZOVIRAX CREAM TO TREAT HERPES LABIALIS IN ADOLESCENTSM01RR000827 · NCRR · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHANG, R JEFFREY · 1985 to 2010
$74.3M
ZONA-FREE HAMSTER OVA ASSAY AS AN INDICATOR OF MALE FERTILITYM01RR000425 · NCRR · LUNDQUIST INSTITUTE FOR BIOMEDICAL INNOVATION AT HARBOR-UCLA MEDICAL CENTER · PI ANDERSON, GAIL V · 1985 to 2011
$74.2M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
LOS ANGELES LATINO EYE STUDYU10EY011753 · NEI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI VARMA, ROHIT · 1998 to 2014
$35.6M
WORKER PROTECTION AGAINST AIRBORNE INFLUENZA - A PILOT STUDYM01RR007122 · NCRR · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI HUNDLEY, WILLIAM GREGORY · 1992 to 2010
$35.2M
Wake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3M
ZUNI KIDNEY PROJECT STUDY I--POPULATION BASED SURVEY OF RENAL DISEASEM01RR000997 · NCRR · UNIVERSITY OF NEW MEXICO · PI ROLDAN, CARLOS A · 1985 to 2010
$30.0M
Building on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6M
Clinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2M
Intramural NIH HHS ZIA AG007380Intramural NIH HHS ZIA EY000401Intramural NIH HHS ZIA EY000403Intramural NIH HHS ZIA EY000408NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NCI NIH HHS N01 CO012400NCRR NIH HHS M01 RR000080NCRR NIH HHS M01 RR000425NCRR NIH HHS M01 RR000827NCRR NIH HHS M01 RR000997NCRR NIH HHS M01 RR001346NCRR NIH HHS M01 RR007122NCRR NIH HHS UL1 RR025005NEI NIH HHS K12 EY016335NEI NIH HHS P30 EY001792NEI NIH HHS P30 EY014104NEI NIH HHS R01 EY014684NEI NIH HHS R01 EY022302NEI NIH HHS R01 EY023644NEI NIH HHS U10 EY011753NHGRI NIH HHS U01 HG004402NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201300046CNHLBI NIH HHS HHSN268201300047CNHLBI NIH HHS HHSN268201300048CNHLBI NIH HHS HHSN268201300049CNHLBI NIH HHS HHSN268201300050CNHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS HHSN268201700001CNHLBI NIH HHS HHSN268201700001INHLBI NIH HHS HHSN268201700002CNHLBI NIH HHS HHSN268201700002INHLBI NIH HHS HHSN268201700003CNHLBI NIH HHS HHSN268201700003INHLBI NIH HHS HHSN268201700004CNHLBI NIH HHS HHSN268201700004INHLBI NIH HHS HHSN268201700005CNHLBI NIH HHS HHSN268201700005INHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC075150NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS N02 HL064278NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS U01 HL041652NHLBI NIH HHS U01 HL041654NHLBI NIH HHS U01 HL065520NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL130114NIA NIH HHS R01 AG023629NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK053591NIDDK NIH HHS R01 DK066358NIDDK NIH HHS R01 DK070941NIDDK NIH HHS R01 DK084149NIDDK NIH HHS R01 DK087914NIDDK NIH HHS U01 DK057249NIDDK NIH HHS U01 DK057292NIDDK NIH HHS U01 DK057295NIDDK NIH HHS U01 DK057298NIDDK NIH HHS U01 DK057300NIDDK NIH HHS U01 DK057303NIDDK NIH HHS U01 DK057304NIDDK NIH HHS U01 DK057329NIDDK NIH HHS U01 DK070657Wellcome TrustWellcome Trust 085475/08/ZWellcome Trust 085475/B/08/Z
6 · The paper itself

Abstract

To identify functionally related genes associated with diabetic retinopathy (DR) risk using gene set enrichment analyses applied to genome-wide association study meta-analyses.

methodsWe analyzed DR GWAS meta-analyses performed on 3246 Europeans and 2611 African Americans with type 2 diabetes. Gene sets relevant to 5 key DR pathophysiology processes were investigated: tissue injury, vascular events, metabolic events and glial dysregulation, neuronal dysfunction, and inflammation. Keywords relevant to these processes were queried in 4 pathway and ontology databases. Two GSEA methods, Meta-Analysis Gene set Enrichment of variaNT Associations (MAGENTA) and Multi-marker Analysis of GenoMic Annotation (MAGMA), were used. Gene sets were defined to be enriched for gene associations with DR if the P value corrected for multiple testing (Pcorr) was <.05.

resultsFive gene sets were significantly enriched for numerous modest genetic associations with DR in one method (MAGENTA or MAGMA) and also at least nominally significant (uncorrected P < .05) in the other method. These pathways were regulation of the lipid catabolic process (2-fold enrichment, Pcorr = .014); nitric oxide biosynthesis (1.92-fold enrichment, Pcorr = .022); lipid digestion, mobilization, and transport (1.6-fold enrichment, P = .032); apoptosis (1.53-fold enrichment, P = .041); and retinal ganglion cell degeneration (2-fold enrichment, Pcorr = .049). The interferon gamma (IFNG) gene, previously implicated in DR by protein-protein interactions in our GWAS, was among the top ranked genes in the nitric oxide pathway (best variant P = .0001).

conclusionsThese GSEA indicate that variants in genes involved in oxidative stress, lipid transport and catabolism, and cell degeneration are enriched for genes associated with DR risk. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Indexed as

Diabetes Mellitus, Type 2Diabetic RetinopathyGenome-Wide Association StudyHumansPolymorphism, Single NucleotideRisk Factors

Identifiers

PMID34166655
PMCPMC8678352
OpenAlexW3175294098

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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.