Evidence map›Paper›PMID 42580338›Full record

ArticleCell2026

Trans-regulatory gene mapping prioritizes disease drivers in asthma.

Isabella M Salamone, Peixin Tian, Zining Qi, Jiaqi Zhao, Li Zhang, Qilong Tan, Jinghui Li, Ashley N Michael, Alexis G Thornburg, Noboru J Sakabe and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

22 authors.

Isabella M SalamoneDepartment of Human Genetics, University of Chicago, Chicago, IL 60637, USA. Electronic address: isalamone@uchicago.edu.
Peixin TianThe First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, P.R. China.
Zining QiCommittee on Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL 60637, USA; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Jiaqi ZhaoSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA; Department of Chemistry, Cornell University, Ithaca, NY 14853, USA; Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.
Li ZhangDepartment of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Qilong TanSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Jinghui LiSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Ashley N MichaelDepartment of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
Alexis G ThornburgDepartment of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Noboru J SakabeDepartment of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Mark MinogueDepartment of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Zachary T WeberDepartment of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Bohao ChenSection of Pulmonary/Critical Care, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
Cezary CiszewskiDepartment of Medicine, University of Chicago, Chicago, IL 60637, USA.
Xin HeDepartment of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Hardik ShahMetabolomics Platform, University of Chicago Comprehensive Cancer Center, Chicago, IL 60637, USA.
Donata VercelliDepartment of Cellular and Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85724, USA.
Carole OberDepartment of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
Hening LinSection of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA; Department of Chemistry, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, University of Chicago, Chicago, IL 60637, USA; Howard Hughes Medical Institute, Chicago, IL, USA.
Zhonghua LiuDepartment of Biostatistics, Columbia University, New York City, NY 10032, USA. Electronic address: zl2509@cumc.columbia.edu.
Marcelo A NóbregaDepartment of Human Genetics, University of Chicago, Chicago, IL 60637, USA. Electronic address: mnobrega@bsd.uchicago.edu.
Xuanyao LiuDepartment of Human Genetics, University of Chicago, Chicago, IL 60637, USA; Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA; Department of Medicine, University of Chicago, Chicago, IL 60637, USA. Electronic address: xuanyao@uchicago.edu.

Funding

Recruitment, Data Collection & Sample Management CoreP01AI148104 · NIAID · UNIVERSITY OF ARIZONA · PI Fernando D Martinez · 2020 to 2026
$19.0M
RESEARCH TRAINING IN RESPIRATORY BIOLOGYT32HL007605 · NHLBI · UNIVERSITY OF CHICAGO · PI Yun Fang, Gokhan M. Mutlu · 1985 to 2026
$18.1M
Tollip inhibits IL-33 signaling during airway influenza virus infectionU19AI125357 · NIAID · UNIVERSITY OF ARIZONA · PI KRAFT, MONICA, VERCELLI, DONATA · 2016 to 2025
$14.7M
MULTIDISCIPLINARY CARDIAC SCIENCEST32HL007381 · NHLBI · UNIVERSITY OF CHICAGO · PI JEANNE M DECARA, Yoav Gilad · 1985 to 2026
$12.5M
Project-003U19AI162310 · NIAID · UNIVERSITY OF CHICAGO · PI Marcelo A. Nobrega, Carole Ober · 2021 to 2026
$10.6M
Statistical Methods to Study the Genetic Basis and Mechanisms of Trans Gene RegulationR35GM138084 · NIGMS · UNIVERSITY OF CHICAGO · PI LIU, XUANYAO · 2020 to 2024
$2.0M
Robust Mendelian Randomization Framework with Multi-Omics Data for Alzheimer's Disease and Related DementiasR01AG086379 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Zhonghua Liu · 2024 to 2026
$1.6M
Statistical methods to link genetic variants to regulatory landscapesR35GM161534 · NIGMS · UNIVERSITY OF CHICAGO · PI Xuanyao Liu · 2026 to 2026
$451k
NHLBI NIH HHS T32 HL007381NHLBI NIH HHS T32 HL007605NIAID NIH HHS P01 AI148104NIAID NIH HHS U19 AI125357NIAID NIH HHS U19 AI162310NIA NIH HHS R01 AG086379NIGMS NIH HHS R35 GM138084NIGMS NIH HHS R35 GM161534
6 · The paper itself

Abstract

Deciphering which genes are most important to disease etiology is a central challenge in human genetics. While genome-wide association studies have cataloged thousands of variants, it's been proposed that most are indirect regulators of a limited, currently unidentified set of central disease-driving genes, defined here as disease-proximal genes (DPGs). Here, we introduce DANDELION, a mediation-inspired statistical framework that prioritizes DPGs by integrating trans-regulatory effects from disease-relevant tissues with gene-level burden from whole-exome sequencing. Applying DANDELION to asthma uncovers novel DPGs that escape detection by conventional methods. CRISPR screens in epithelial and T cells find that most DPGs regulate key asthma-related cellular phenotypes. We also demonstrate that loss of two DPGs, SLC27A3 and SCD, affects inflammation and airway remodeling in a mouse model of allergic asthma. Our study establishes DANDELION as a powerful framework for prioritizing novel, therapeutically actionable genes and pathways underlying disease pathogenesis.

Indexed as

AsthmaChromosome MappingAirway RemodelingAnimalsDisease Models, AnimalExome SequencingFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMiceMice, Inbred C57BLasthmacomplex traitstrans-gene regulation

Identifiers

PMID42580338
PMCPMC13496006

What OpenQuestion holds

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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 OpenQuestion graph.