Evidence map›Paper›PMID 35986912›Full record

ArticleThe Journal of infectious diseases2022

DDX58 Is Associated With Susceptibility to Severe Influenza Virus Infection in Children and Adolescents.

Sanghun Lee, Yu Zhang, Margaret Newhams, Tanya Novak, Paul G Thomas, Peter M Mourani, Mark W Hall, Laura L Loftis, Natalie Z Cvijanovich, Keiko M Tarquinio and 21 more

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

Article in The Journal of infectious diseases, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

7 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. The potential impacts of human genetics on virus emergence.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  5. Cell-Autonomous Immunity: From Cytosolic Sensing to Self-Defense.International journal of molecular sciences · 2025
    Review
  6. Review
  7. Article
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

31 authors at 20 institutions in 2 countries.

Sanghun LeeDepartment of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.ORCID 0000-0002-0573-9555
Yu ZhangLaboratory of Clinical Immunology and Microbiology, Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Margaret NewhamsDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
Tanya NovakDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
Paul G ThomasDepartment of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee, USA.
Peter M MouraniSection of Critical Care Medicine, Department of Pediatrics, University of Arkansas for Medical Sciences and Arkansas Children's Research Institute, Little Rock, Arkansas, USA.
Mark W HallDivision of Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio, USA.
Laura L LoftisSection of Critical Care Medicine, Department of Pediatrics, Texas Children's Hospital, Houston, Texas, USA.
Natalie Z CvijanovichDivision of Critical Care Medicine, UCSF Benioff Children's Hospital Oakland, Oakland, California, USA.
Keiko M TarquinioDivision of Critical Care Medicine, Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia, USA.
Adam J SchwarzDepartment of Pediatrics, Children's Hospital of Orange County, Orange, California, USA.
Scott L WeissDivision of Critical Care, Department of Anesthesiology and Critical Care, The University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
Neal J ThomasDepartment of Pediatrics, Penn State Hershey Children's Hospital, Penn State University College of Medicine, Hershey, Pennsylvania, USA.
Barry MarkovitzDepartment of Anesthesiology Critical Care Medicine, Children's Hospital Los Angeles, Los Angeles, California, USA.
Melissa L CullimoreDivision of Pediatric Critical Care, Department of Pediatrics, University of Nebraska Medical Center, Omaha, Nebraska, USA.
Ronald C SandersSection of Pediatric Critical Care, Department of Pediatrics, Arkansas Children's Hospital, Little Rock, Arkansas, USA.
Matt S ZinterDivisions of Critical Care Medicine and Allergy, Immunology, and Bone Marrow Transplant, Department of Pediatrics, University of California, San Francisco, San Francisco, California, USA.
Janice E SullivanDivision of Pediatric Critical Care, University of Louisville School of Medicine and Norton Children's Hospital, Louisville, Kentucky, USA.
Natasha B HalasaDivision of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Melania M BembeaDepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
John S GiulianoDivision of Critical Care, Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut, USA.
Katri V TyppoDepartment of Pediatrics, Steele Children's Research Center, University of Arizona, Tucson, Arizona, USA.
Ryan A NofzigerDivision of Critical Care Medicine, Department of Pediatrics, Akron Children's Hospital, Akron, Ohio, USA.
Steven L SheinDivision of Pediatric Critical Care Medicine, Rainbow Babies and Children's Hospital, Cleveland, Ohio, USA.
Michele KongDivision of Pediatric Critical Care Medicine, Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Bria M CoatesDivision of Critical Care Medicine, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
Scott T WeissChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Christoph LangeDepartment of Biostatistics, T. H. Chan School of Public Health, Harvard University, Boston, Massachusetts, USA.
Helen C SuLaboratory of Clinical Immunology and Microbiology, Intramural Research Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Adrienne G RandolphDepartment of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.ORCID 0000-0002-3084-3071
Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Pediatric Intensive Care Influenza (PICFlu) Investigators and the Trans-Omics for Precision Medicine (TOPMed) Investigators
Boston Children's Hospital · USBrigham and Women's Hospital · USArkansas Children's Hospital · USNational Institutes of Health · USAkron Children's Hospital · USChildren's Hospital of Los Angeles · USChildren's Hospital of Orange County · USEmory University · USHarvard University · USJohns Hopkins University · USNationwide Children's Hospital · USNorthwestern University · USPenn State Milton S. Hershey Medical Center · USRainbow Babies & Children's Hospital · USSt. Jude Children's Research Hospital · USTexas Children's Hospital · USUCSF Benioff Children's Hospital · USUniversity of Alabama at Birmingham · USUniversity of Arizona · USUniversity of California, San Francisco · US

Funding

The Genetic Epidemiology of Asthma in Costa RicaR37HL066289 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI WEISS, SCOTT T · 2007 to 2015
$14.6M
Finding Genomic Profiles of COVID-19 Phenotypes from the EHRU01HG008685 · NHGRI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIZABETH W KARLSON, Matthew S Lebo · 2015 to 2026
$13.6M
Systems Biology of Airway DiseaseP01HL132825 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI WEISS, SCOTT T · 2016 to 2020
$12.6M
Studies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
Rare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6M
Immunobiology of Influenza Virus-related Critical Illness in Young HostsR01AI154470 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI RANDOLPH, ADRIENNE G, THOMAS, PAUL G. · 2020 to 2024
$4.7M
Genetic Epidemiology of Life-Threatening Influenza in ChildrenR01AI084011 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI RANDOLPH, ADRIENNE G · 2010 to 2013
$3.1M
Genetic Epidemiology of Life-Threatening Influenza Infection in ChildrenR56AI084011 · NIAID · BOSTON CHILDREN'S HOSPITAL · PI RANDOLPH, ADRIENNE G · 2009 to 2009
$712k
NHGRI NIH HHS U01 HG008685NHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS P01 HL132825NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R37 HL066289NHLBI NIH HHS U01 HL120393NIAID NIH HHS R01 AI084011NIAID NIH HHS R01 AI154470NIAID NIH HHS R56 AI084011NIH HHS AI154470
6 · The paper itself

Abstract

backgroundSeasonal influenza virus infection causes a range of disease severity, including lower respiratory tract infection with respiratory failure. We evaluated the association of common variants in interferon (IFN) regulatory genes with susceptibility to critical influenza infection in children.

methodsWe performed targeted sequencing of 69 influenza-associated candidate genes in 348 children from 24 US centers admitted to the intensive care unit with influenza infection and lacking risk factors for severe influenza infection (PICFlu cohort, 59.4% male). As controls, whole genome sequencing from 675 children with asthma (CAMP cohort, 62.5% male) was compared. We assessed functional relevance using PICFlu whole blood gene expression levels for the gene and calculated IFN gene signature score.

resultsCommon variants in DDX58, encoding the retinoic acid-inducible gene I (RIG-I) receptor, demonstrated association above or around the Bonferroni-corrected threshold (synonymous variant rs3205166; intronic variant rs4487862). The intronic single-nucleotide polymorphism rs4487862 minor allele was associated with decreased DDX58 expression and IFN signature (P < .05 and P = .0009, respectively) which provided evidence supporting the genetic variants' impact on RIG-I and IFN immunity.

conclusionsWe provide evidence associating common gene variants in DDX58 with susceptibility to severe influenza infection in children. RIG-I may be essential for preventing life-threatening influenza-associated disease.

Indexed as

Communicable DiseasesInfluenza, HumanAdolescentChildDEAD Box Protein 58FemaleHumansInterferonsMalePolymorphism, Single NucleotideReceptors, ImmunologicDEAD Box Protein 58InterferonsReceptors, ImmunologicRIGI protein, humanDDX58host geneticspediatric influenzaRIG-I receptorsusceptibility

Identifiers

PMID35986912
PMCPMC10205622
OpenAlexW4292440656

What Socratic holds

Textmetadata
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.