Evidence map›Paper›PMID 40034775›Full record

ArticlemedRxiv : the preprint server for health sciences2024

Genetic contributions to epigenetic-defined endotypes of allergic phenotypes in children.

Emma E Thompson, Xiaoyuan Zhong, Peter Carbonetto, Andréanne Morin, Jason Willwerscheid, Cynthia M Visness, Leonard B Bacharier, Meyer Kattan, George T O'Connor, Katherine Rivera-Spoljaric and 16 more

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors.

Emma E ThompsonDepartment of Human Genetics, University of Chicago, Chicago IL.
Xiaoyuan ZhongDepartment of Human Genetics, University of Chicago, Chicago IL.
Peter CarbonettoDepartment of Human Genetics, University of Chicago, Chicago IL.
Andréanne MorinDepartment of Human Genetics, University of Chicago, Chicago IL.
Jason WillwerscheidDepartment of Mathematics & Computer Science, Providence College, Providence, RI.
Cynthia M VisnessRho Inc., Federal Research Operations, Durham, NC.
Leonard B BacharierDepartment of Pediatric Allergy, Immunology and Pulmonary Medicine, Monroe Carell Jr Children's Hospital at Vanderbilt University Medical Center, Nashville TN.
Meyer KattanDepartment of Pediatrics, Columbia University Medical Center, New York NY.
George T O'ConnorPulmonary Center, Boston University School of Medicine, Boston MA.
Katherine Rivera-SpoljaricDepartment of Pediatrics, Washington University School of Medicine, St. Louis, MO.
Robert A WoodDepartment of Pediatrics, Johns Hopkins University, Baltimore MD.
Diane R GoldDepartment of Environmental Health, Harvard T.H. Chan School of Public Health; Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Gurjit K Khurana HersheyDivision of Asthma Research, Cincinnati Children's Hospital and Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati OH.
Christine C JohnsonDepartment of Public Health Sciences, Henry Ford Health, Detroit MI.
Rachel L MillerDivision of Clinical Immunology, Icahn School of Medicine at Mount Sinai, New York, NY.
Christine M SeroogyDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison WI.
Edward M ZorattiDivision of Allergy and Clinical Immunology, Henry Ford Health, Detroit MI.
Peter J GergenNational Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD.
Albert M LevinDepartment of Public Health Sciences, Henry Ford Health, Detroit MI.
Matthew C AltmanSystems Immunology Division, Benaroya Research Institute Systems and Department of Medicine, University of Washington, Seattle WA.
Tina HartertDepartment of Medicine, Vanderbilt University School of Medicine, Nashville TN.
Matthew StephensDepartment of Human Genetics, University of Chicago, Chicago IL.
Daniel J JacksonDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison WI.
James E GernDepartment of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison WI.
Christopher G McKennanDepartment of Statistics, University of Pittsburgh, Pittsburgh, PA.
Carole OberDepartment of Human Genetics, University of Chicago, Chicago IL.

Funding

Vanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7M
WU INSTITUTE OF CLINICAL AND TRANSLATIONAL SCIENCESUL1TR002345 · NCATS · WASHINGTON UNIVERSITY · PI William G. Powderly · 2017 to 2026
$97.8M
Inner City Asthma consortium 3 (ICAC3)UM1AI114271 · NIAID · UNIVERSITY OF WISCONSIN-MADISON · PI GERN, JAMES E., JACKSON, DANIEL J · 2014 to 2021
$79.4M
Wisconsin Infant Study Cohort (WISC) ECHO Pediatric Follow-UpUH3OD023282 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI James E. Gern · 2018 to 2026
$64.8M
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1M
CTSA INFRASTRUCTURE FOR PEDIATRIC RESEARCHUL1RR024156 · NCRR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2006 to 2011
$53.0M
Washington University Institute of Clinical and Translational Sciences (UL1)UL1RR024992 · NCRR · WASHINGTON UNIVERSITY · PI EVANOFF, BRADLEY A · 2007 to 2011
$45.4M
True Metal fac coreP30ES009089 · NIEHS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Steven N. Chillrud · 1998 to 2026
$44.7M
ZIPRASIDONE (GEODON) AUGMENTATION IN SEROTONIN REUPTAKE INHIBITOR-RESISTANT OBM01RR000071 · NCRR · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI KOLEVZON, ALEXANDER · 1985 to 2009
$41.5M
ZINC AND CA EDTA THERAPY OF PLUMBISMM01RR000052 · NCRR · JOHNS HOPKINS UNIVERSITY · PI VINING, EILEEN PATRICE · 1985 to 2007
$37.3M
Viral and Host Determinants of Infant and Childhood Allergy and AsthmaU19AI095227 · NIAID · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Tina V Hartert · 2011 to 2026
$34.9M
Virus-Bacterial Interactions and Exacerba of AsthmaP01HL070831 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI BOCHKOV, YURY A · 2002 to 2017
$31.3M
NCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR002243NCATS NIH HHS UL1 TR002345NCRR NIH HHS M01 RR000052NCRR NIH HHS M01 RR000071NCRR NIH HHS M01 RR000533NCRR NIH HHS UL1 RR024156NCRR NIH HHS UL1 RR024992NCRR NIH HHS UL1 RR025771NHGRI NIH HHS R01 HG002585NHGRI NIH HHS R56 HG002585NHLBI NIH HHS P01 HL070831NHLBI NIH HHS R01 HL113010NHLBI NIH HHS U10 HL064305NIAID NIH HHS HHSN272200900052CNIAID NIH HHS HHSN272201000052INIAID NIH HHS K01 AI070606NIAID NIH HHS N01 AI025482NIAID NIH HHS N01 AI025496NIAID NIH HHS P01 AI089473NIAID NIH HHS R01 AI035786NIAID NIH HHS R01 AI050681NIAID NIH HHS R01 AI051598NIAID NIH HHS R01 AI060040NIAID NIH HHS R01 AI061774NIAID NIH HHS R01 AI110450NIAID NIH HHS R21 AI059415NIAID NIH HHS R21 AI069271NIAID NIH HHS R21 AI080066NIAID NIH HHS R37 AI060040NIAID NIH HHS R56 AI050681NIAID NIH HHS U19 AI095227NIAID NIH HHS U19 AI095230NIAID NIH HHS UM1 AI114271NIA NIH HHS R01 AG080590NICHD NIH HHS R01 HD061879NICHD NIH HHS R01 HD082147NIEHS NIH HHS P01 ES009600NIEHS NIH HHS P30 ES009089NIEHS NIH HHS R01 ES008977NIEHS NIH HHS R01 ES011170NIEHS NIH HHS R01 ES013163NIEHS NIH HHS R01 ES019890NIEHS NIH HHS R21 ES022321NIH HHS UG3 OD023282NIH HHS UH3 OD023282NIMH NIH HHS R01 MH061879
6 · The paper itself

Abstract

Background: Asthma is the most common chronic respiratory disease in children, but little is known about genetic contributions to its underlying endotypes. To address this gap, we studied the methylome, transcriptome, and genome from children with extensive phenotyping from birth. Methods: We performed DNA methylation (DNAm) studies using the Asthma&Allergy array and RNA-sequencing in nasal mucosal cells from 284 children (age 11 years) in the Urban Environment and Childhood Asthma (URECA) birth cohort with genotypes from whole-genome sequencing. Using empirical Bayes matrix factorization on all CpGs on the array, we derived 16 DNAm signatures and tested for associations between phenotypes and gene expression. We then replicated results in two additional cohorts and estimated the heritability of phenotype-associated signatures using single-nucleotide polymorphisms (SNPs) associated with an allergic disease, and with CpGs and genes associated with the signatures. Findings: Three DNAm signatures were associated with at least one phenotype: allergic asthma, allergic rhinitis, allergic sensitization (atopy), total IgE, exhaled nitric oxide, or blood eosinophils. The genes correlated with each of the three signatures were enriched in networks reflecting inhibited immune response to microbes, impaired epithelial barrier integrity, and activated T2 immune pathways. We replicated the signature-phenotype associations in two additional birth cohorts. The estimated joint SNP heritabilities of the signatures were 0.17 (p=0.0027), 0.30 (p=9.3×10 Interpretation: We identified three significantly heritable DNAm signatures defining asthma and allergy endotypes across diverse populations. Our study demonstrated that epigenetic patterning in airway mucosal cells reflects perturbations in underlying biological processes related to the development of asthma and allergic diseases in childhood. Funding: National Institute of Allergy and Infectious Diseases and the National Institutes of Health, Office of the Director.

Identifiers

PMID40034775
PMCPMC11875257

What Socratic holds

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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 Socratic graph.