Evidence map›Paper›PMID 41351491›Full record

ArticleAllergy2026

Mediation of Polygenic Asthma Risk Through Gene Expression.

Rakesh Natarajan, Brooke Szczesny, Kanika Kanchan, Erika Esquinca, Meher Preethi Boorgula, Sameer Chavan, Monica Campbell, Wendy Lorizio, Ayo P Doumatey, Alvaro A Cruz and 20 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Allergy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Cumulative genetic risk for asthma contributes to disease severity in children with asthma.The journal of allergy and clinical immunology. Global · 2026
    Article
  3. 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

30 authors.

Rakesh NatarajanGenomics and Precision Health Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Brooke SzczesnyGenomics and Precision Health Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Kanika KanchanGenomics and Precision Health Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Erika EsquincaDepartment of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Meher Preethi BoorgulaDepartment of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
Sameer ChavanDepartment of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Monica CampbellDepartment of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Wendy LorizioDepartment of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Ayo P DoumateyCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
Alvaro A CruzFundacao ProAR and Federal University of Bahia, Salvador, Bahia, Brazil.ORCID https://orcid.org/0000-0002-7403-3871
Harold WatsonFaculty of Medical Sciences, The University of the West Indies, Queen Elizabeth Hospital, St. Michael, Bridgetown, Barbados.
Edward T NaureckasDepartment of Medicine, University of Chicago, Chicago, Illinois, USA.
B Louise GilesDepartment of Pediatrics, University of Chicago, Chicago, Illinois, USA.
Ganiyu ArinolaDepartment of Immunology, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Olumide SogaoluDepartment of Medicine, College of Medicine, University of Ibadan, Ibadan, Nigeria.
Adegoke G FaladeDepartment of Pediatrics, University of Ibadan, Ibadan, Nigeria.
Nadia N HanselDepartment of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Christopher O OlopadeDepartment of Medicine, University of Chicago, Chicago, Illinois, USA.
Charles N RotimiCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
R Clive LandisEdmund Cohen Laboratory for Vascular Research, George Alleyne Chronic Disease Research Centre, Caribbean Institute for Health Research, The University of the West Indies, Cave Hill Campus, Wanstead, Barbados.
Camila A FigueiredoInstituto de Ciências de Saúde, Universidade Federal da Bahia, Salvador, Brazil.ORCID https://orcid.org/0000-0003-1356-6188
Eimear E KennyCenter for Genomic Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Ingo RuczinskiDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Andrew H LiuDepartment of Pediatrics, Childrens Hospital Colorado and University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
Carole OberDepartment of Human Genetics, University of Chicago, Chicago, Illinois, USA.
Margaret A TaubDepartment of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Randi K JohnsonDepartment of Biomedical Informatics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Kathleen C BarnesDepartment of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, Colorado, USA.
Genevieve L WojcikDepartment of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA.
Rasika A MathiasGenomics and Precision Health Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Funding

New Approaches for Empowering Studies of Asthma in Populations of African DescentR01HL104608 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI BARNES, KATHLEEN C, KENNY, EIMEAR ELIZABETH · 2011 to 2022
$23.1M
Pilot Program CoreP30ES027792 · NIEHS · UNIVERSITY OF CHICAGO · PI Gokhan M. Mutlu, Gail S Prins · 2017 to 2026
$13.6M
National Institute of Allergy and Infectious DiseasesNational Institutes of Health (NIH) R01HL104608NHLBI NIH HHSNIEHS NIH HHS P30 ES027792
6 · The paper itself

Abstract

backgroundExisting asthma polygenic risk scores (PRSs) have minimal validation in African-ancestry populations, leaving gaps in our understanding of the wide applicability of PRSs. To widen our understanding of the applicability of asthma PRSs, we apply published PRSs in African-ancestry individuals and quantify the extent to which the PRS-asthma relationship is mediated by clinical biomarkers and gene-expression signatures of asthma.

methodsWe applied 22 PRSs from the PGS Catalog in 673 individuals from the Consortium on Asthma among African-Ancestry Populations in the Americas (CAAPA) and calculated the percent of the PRS-asthma relationship that is statistically mediated by clinical and nasal epithelium transcriptomic biomarkers of asthma. Asthma case/control status was defined as ever/never having a doctor's diagnosis of disease. For gene expression mediation analysis, we limited the cases to those with current disease.

resultsThe PRS (PGS001782) created by the Global Biobank Meta-analysis Initiative (N = 32,658 individuals of African ancestry) performed the best (ΔAUC = 0.104, AUC = 0.657) adjusted for age, sex, study site, and the first two genetic principal components (PC1-2). The PRS's effect on asthma was mediated by total IgE (tIgE) (38.8%, p.adj < 0.0002), multi-allergen ImmunoCAP phadiatop specific IgE (sIgE) (38.7%, p.adj < 0.0002), and eosinophils (7.3%, p.adj = 0.004). Mediation was observed for gene expression modules related to T2 inflammation (21.9%, p.adj < 0.0024), wound healing (11.9%, p.adj = 0.008), and medication response (6.8%, p.adj = 0.049).

conclusionWe found the best PRS to be the one derived using the largest sample size and including African-ancestry individuals. Mediation supports the well-documented biology of T2 inflammation in asthma as well as pathophysiological components of asthma like wound healing and medication response.

Indexed as

AsthmaGene ExpressionGene Expression RegulationGenetic Predisposition to DiseaseMultifactorial InheritanceAdultBiomarkersFemaleHumansMaleMiddle AgedRisk FactorsTranscriptomeBiomarkersAfrican ancestriesasthmaeosinophilsgene expressionGWASIgEmedication responsepolygenic risk scoresT2 inflammationwound healing

Identifiers

PMID41351491
PMCPMC13040662

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.