Evidence map›Paper›PMID 40010152›Full record

ArticleEBioMedicine2025

Identifying chronic obstructive pulmonary disease subtypes using multi-trait genetics.

Andrey Ziyatdinov, Brian D Hobbs, Samir Kanaan-Izquierdo, Matthew Moll, Phuwanat Sakornsakolpat, Nick Shrine, Jing Chen, Kijoung Song, Russell P Bowler, Peter J Castaldi and 6 more

Registry-linked trialAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00608764 (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease), which is not on this map. Cited by 5 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed, 1 pooled it
–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.

NCT00608764 active not recruitingnot on this map

Genetic Epidemiology of Chronic Obstructive Pulmonary Disease (COPDGene)

TypeobservationalSponsorBrigham and Women's HospitalRan2007 to 2028Enrolled10,718ConditionsPulmonary Disease, Chronic Obstructive, Emphysema, Bronchitis, Chronic
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. UBE2M deficiency in alveolar macrophages promotes emphysema through HIF-2α/MMP12 axis.Chinese medical journal pulmonary and critical care medicine · 2026
    Article
  3. Review
  4. Article
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Andrey ZiyatdinovDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Brian D HobbsChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Samir Kanaan-IzquierdoCentre de Recerca en Enginyeria Biomèdica, Universitat Politècnica de Catalunya, Barcelona 08028, Spain; CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Catalonia, Spain; Institut de Recerca Sant Joan de Deu, Esplugues de Llobregat, Spain.
Matthew MollChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Phuwanat SakornsakolpatChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Nick ShrineDepartment of Health Sciences, University of Leicester, Leicester, UK.
Jing ChenDepartment of Health Sciences, University of Leicester, Leicester, UK.
Kijoung SongHuman Genetics, GlaxoSmithKline, Collegeville, PA, USA.
Russell P BowlerDivision of Pulmonary and Critical Care, Dept. Med, National Jewish Health, Denver, CO, USA.
Peter J CastaldiChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Martin D TobinDepartment of Health Sciences, University of Leicester, Leicester, UK; National Institute for Health Research, Leicester Respiratory Biomedical Research Centre, Glenfield Hospital, Leicester, UK.
Peter KraftDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Edwin K SilvermanChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Hanna JulienneInstitut Pasteur, Université Paris Cité, Department of Computational Biology, Paris F-75015, France.
Michael H ChoChanning Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Hugues AschardDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Institut Pasteur, Université Paris Cité, Department of Computational Biology, Paris F-75015, France. Electronic address: hugues.aschard@pasteur.fr.

Funding

Genetic Epidemiology of COPDU01HL089897 · NHLBI · NATIONAL JEWISH HEALTH · PI CRAPO, JAMES D · 2007 to 2021
$56.9M
Genetic Epidemiology of COPDU01HL089856 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2007 to 2021
$20.7M
(2 of 2) Genetic Epidemiology of COPDR01HL089856 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2012 to 2016
$18.9M
Genetic and Genomic Characterization of the Occurrence and Progression of Interstitial Lung AbnormalitiesR01HL135142 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI MICHAEL H. CHO, GARY MATTHEW HUNNINGHAKE · 2017 to 2026
$7.7M
Using Integrative Genomics To Identify and Characterize Emphysema-Associated eQTLR01HL124233 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI CASTALDI, PETER · 2014 to 2024
$7.1M
Genetic and Functional Dissection of a Cluster of COPD GWAS Signals on Chromosome 4qR01HL147148 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI CHO, MICHAEL H., SILVERMAN, EDWIN K · 2019 to 2022
$3.5M
Identifying functional variants in COPD GWAS lociR01HL137927 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI CHO, MICHAEL H., SILVERMAN, EDWIN K · 2017 to 2020
$3.5M
Clinical Implications, Genomics, and Transcriptions of Mucus Plugging in SmokersR01HL149861 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI CHO, MICHAEL H., DIAZ, ALEJANDRO · 2020 to 2023
$3.2M
Genetic variants that affect the airway epithelium to drive obstructive lung diseaseR01HL166992 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Peter Castaldi, Yohannes Tesfaigzi · 2024 to 2026
$2.6M
COPD GWAS Functional Variant Identification in Airway Epithelial Cells using Deep Learning Splicing ModelsR01HL171213 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Peter Castaldi, Yohannes Tesfaigzi · 2024 to 2026
$2.3M
NHLBI NIH HHS R01 HL089856NHLBI NIH HHS R01 HL124233NHLBI NIH HHS R01 HL135142NHLBI NIH HHS R01 HL137927NHLBI NIH HHS R01 HL147148NHLBI NIH HHS R01 HL149861NHLBI NIH HHS R01 HL166992NHLBI NIH HHS R01 HL171213NHLBI NIH HHS U01 HL089856NHLBI NIH HHS U01 HL089897Wellcome Trust 225221
6 · The paper itself

Abstract

backgroundChronic Obstructive Pulmonary Disease (COPD) has a broad spectrum of clinical characteristics. The aetiology of these differences is not well understood. The objective of this study is to assess whether respiratory genetic variants cluster by phenotype and associate with COPD heterogeneity.

methodsWe clustered genome-wide association studies of COPD, lung function, and asthma and phenotypes from the UK Biobank using non-negative matrix factorization. We constructed cluster-specific genetic risk scores and tested these scores for association with phenotypes in non-Hispanic white subjects in the COPDGene study.

findingsWe identified three clusters from 482 variants and 44 traits from genetic associations in 379,337 UK Biobank participants. Variants from asthma, COPD, and lung function were found in all three clusters. Clusters displayed varying effects on white blood cell counts, height, and body mass index (BMI)-related phenotypes in the UK Biobank. In the COPDGene cohort, cluster-specific genetic risk scores were associated with differences in steroid use, BMI, lymphocyte counts, and chronic bronchitis, as well as variations in gene and protein expression.

interpretationOur results suggest that multi-phenotype analysis of obstructive lung disease-related risk variants may identify genetically driven phenotypic patterns in COPD.

fundingMHC was supported by R01HL149861, R01HL135142, R01HL137927, R01HL147148, and R01HL089856. HA and HJ were supported by ANR-20-CE36-0009-02 and ANR-16-CONV-0005. The COPDGene study (NCT00608764) is supported by grants from the NHLBI (U01HL089897 and U01HL089856), by NIH contract 75N92023D00011, and by the COPD Foundation through contributions made to an Industry Advisory Committee that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer and Sunovion.

Indexed as

Genetic Predisposition to DiseasePulmonary Disease, Chronic ObstructiveQuantitative Trait, HeritableAgedAsthmaCluster AnalysisFemaleGenome-Wide Association StudyHumansMaleMiddle AgedPhenotypePolymorphism, Single NucleotideUnited KingdomWhite PeopleCOPDGenetic epidemiologyMultitrait analysisPathways

Identifiers

PMID40010152
PMCPMC11905855

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

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.