Evidence mapPaperPMID 41935671Full record

ArticleThe Journal of allergy and clinical immunology2026

Context-specific genetic effects inform endotypes and treatment in asthma.

Andy Dahl, Satria Sajuthi, Nadav Rappaport, Joshua Galanter, Chris Gignoux, Esteban Burchard, Max Seibold, Noah Zaitlen

Abstract read
In one paragraph

Article in The Journal of allergy and clinical immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing 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

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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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

8 authors.

Andy DahlDepartment of Medicine, Section of Genetic Medicine, University of Chicago, Chicago, Ill. Electronic address: andywdahl@uchicago.edu.
Satria SajuthiDepartment of Pediatrics, National Jewish Health, Denver, Colo.
Nadav RappaportDepartment of Software and Information Systems Engineering, Ben-Gurion University of the Negev, Beersheba, Israel.
Joshua GalanterEarly Clinical Development, Genentech, South San Francisco, Calif.
Chris GignouxColorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colo.
Esteban BurchardDepartment of Medicine, University of California, San Francisco, Calif.
Max SeiboldDepartment of Pediatrics, National Jewish Health, Denver, Colo.
Noah ZaitlenDepartment of Neurology, University of California, Los Angeles, Calif.

Funding

Improved methods for inference of genotype-specific response to environmental toxinsR01ES029929 · NIEHS · PRINCETON UNIVERSITY · PI Julien Ayroles, ANDREW G CLARK · 2022 to 2023
$1.4M
Leveraging genetic variation to dissect gene regulatory networks of reprogramming to pluripotencyU01HG012079 · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2025 to 2025
$931k
Novel statistical genetics methods to unravel polygenic interactions in complex traitsR35GM150822 · UNIVERSITY OF CHICAGO · 2025 to 2025
$401k
NHGRI NIH HHS R01 HG011345NHGRI NIH HHS U01 HG012079NHLBI NIH HHS K25 HL157603NIEHS NIH HHS R01 ES029929NIGMS NIH HHS R35 GM150822
6 · The paper itself

Abstract

backgroundAsthma has heterogeneous risk factors, subtypes, and treatments. It is often unclear how to stratify this heterogeneity in scientific studies and clinical care. Genetics could explain root causes of this clinical heterogeneity, called endotypes, but prior studies have used models that are not designed for complex diseases like asthma.

objectiveWe aimed to find genetic effects that partly explain different asthma endotypes.

methodsWe used recent powerful and robust statistical models of context-specific genetic effects in complex traits. We identified genetic subtypes by clustering clinical asthma features in a case-control cohort, GALA II. We replicated the genetic endotypes in the UK Biobank with gene-context interaction tests.

resultsAsthma-associated single nucleotide polymorphisms, polygenic scores, and genome-wide heritability revealed subtype-specific genetic endotypes correlated with type 2 inflammation, allergy, and neuroticism. We validated the type 2 associations with molecular data including nasal RNA sequencing. In the UK Biobank, we replicated these endotypes and found they interact with several polygenic scores and drug-relevant genes.

conclusionOur results show how context-specific genetic effects can unravel biomedically meaningful endotypes of complex disease and suggest novel precision treatment strategies.

Indexed as

AsthmaCase-Control StudiesFemaleGenetic Predisposition to DiseaseGenetic Risk ScoreGenome-Wide Association StudyHumansMaleMultifactorial InheritancePhenotypePolymorphism, Single NucleotideAsthmaendotypegenetic associationgenetic interactionsubtypetype 2 inflammation

Identifiers

PMID41935671
PMCPMC13218556

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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.