Evidence map›Paper›PMID 41419234›Full record

ArticleBMJ open respiratory research2025

Epigenomic study of the lower airway reveals COPD-associated methylation patterns and potential microbiota links.

Shuo Cao, Abhishek Shrivastav, Eugene R Bleecker, Siddharth Madapoosi, John Erb-Downward, Joe Zein, Xianfeng Chen, Timothy D Howard, Gregory A Hawkins, Igor Z Barjaktarevic and 23 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMJ open respiratory research, 2025. 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

33 authors.

Shuo CaoMayo Clinic Arizona, Scottsdale, Arizona, USA.ORCID http://orcid.org/0009-0009-3414-9616
Abhishek ShrivastavMayo Clinic, Scottsdale, Arizona, USA.
Eugene R BleeckerMayo Clinic, Scottsdale, Arizona, USA.
Siddharth MadapoosiUniversity of Michigan, Ann Arbor, Michigan, USA.
John Erb-DownwardUniversity of Michigan, Ann Arbor, Michigan, USA.
Joe ZeinMayo Clinic, Scottsdale, Arizona, USA.
Xianfeng ChenMayo Clinic, Scottsdale, Arizona, USA.
Timothy D HowardWake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Gregory A HawkinsWake Forest School of Medicine, Winston-Salem, North Carolina, USA.
Igor Z BarjaktarevicUniversity of California Los Angeles, Los Angeles, California, USA.ORCID http://orcid.org/0000-0002-8096-0858
Russell BowlerCleveland Clinic, Cleveland, Ohio, USA.
Robert Graham BarrColumbia University Medical Center, New York, New York, USA.
Alejandro ComellasInternal Medicine, University of Iowa, Iowa, Iowa, USA.ORCID http://orcid.org/0000-0003-1521-7520
Christopher B CooperUniversity of California Los Angeles, Los Angeles, California, USA.
David CouperBiostatistics, University of North Carolina, Chapel Hill, North Carolina, USA.
Meilan HanPulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA.ORCID http://orcid.org/0000-0002-9095-4419
Nadia N HanselMedicine, Johns Hopkins University, Baltimore, Maryland, USA.
Annette T HastieCenter for Genomics and Personalized Medicine Research, Wake Forest Health Sciences, Winston Salem, North Carolina, USA.
Robert KanerInstitute of Genetic Medicine, Weill Cornell Medical College, New York, New York, USA.
Richard E KannerMedicine, University of Utah, Salt Lake City, Utah, USA.
Victor KimDivision of Pulmonary and Critical Care Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA.ORCID http://orcid.org/0000-0002-1385-1571
Fernando J MartinezUniversity of Massachusetts, Worcester, Massachusetts, USA.
Wendy C MooreCenter for Genomics and Personalized Medicine Research, Wake Forest Health Sciences, Winston Salem, North Carolina, USA.
Wanda K O'NealCystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina, Chapel Hill, North Carolina, USA.
Robert PaineInternal Medicine/Pulmonary and Critical Care, University of Utah, Salt Lake City, Utah, USA.
Benjamin SmithDepartment of Medicine, Columbia University, New York, New York, USA.
Eric A HoffmanRadiology, University of Iowa, Iowa City, Iowa, USA.
Deborah A MeyersMayo Clinic, Scottsdale, Arizona, USA.
Prescott G WoodruffUniversity of California San Francisco, San Francisco, California, USA.
Stephanie ChristensonMedicine, University of California San Francisco, San Francisco, California, USA.
Jeffrey L CurtisInternal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Yvonne Jean HuangUniversity of Michigan, Ann Arbor, Michigan, USA.ORCID http://orcid.org/0000-0002-7497-6597
Victor E OrtegaMayo Clinic, Scottsdale, Arizona, USA Ortega.Victor@mayo.edu.

Funding

The Impact of Biological Sex on Asthma OutcomesR01HL161674 · NHLBI · MAYO CLINIC ARIZONA · PI Joe Zein · 2023 to 2026
$1.5M
NHLBI NIH HHS R01 HL161674
6 · The paper itself

Abstract

introductionDespite the identification of multiple susceptibility loci by genome-wide association studies (GWAS), considerable chronic obstructive pulmonary disease (COPD) heritability remains unexplained.

aimTo identify interaction networks of airway epithelial cell DNA methylation in COPD and further explore potential correlations with airway bacterial composition, as potentially collective regulators of biological pathways influencing COPD severity.

methodsUsing DNA isolated from bronchial airway brushings of 67 ever-smokers (>20 pack-years) from the SubPopulations and InteRmediate Outcomes Measures in COPD Study (SPIROMICS), we assessed proportion of DNA methylation (β) by epigenome-wide association study (EWAS) and examined associations of differentially methylated CpG probes (DMPs) with risk for moderate-to-severe COPD (N=34) versus absent or mild COPD (N=33). We tested co-methylation modules generated by Weighted Correlation Network Analyses (WGCNA) for associations with moderate-to-severe COPD and with bacterial genus-level relative abundances (16S rRNA sequencing).

resultsEWAS-identified nominally significant DMPs enriched for lung function GWAS loci. Eigengenes in six WGCNA modules were associated with moderate-to-severe COPD (false discovery rate <0.05). Four of those modules were enriched for forced expiratory volume in 1 s/forced vital capacity GWAS loci, and five overlapped with DMPs from EWAS. Overlapping CpG loci in three COPD-associated modules were adjacent to mucin genes; one had 10 genes highly ranked by connectivity with

conclusionsBronchial epithelial DNA methylation modules enriched for lung function GWAS loci associate with COPD severity in SPIROMICS. Potential module relationships to bronchial bacterial composition require further validation.

Indexed as

DNA MethylationMicrobiotaPulmonary Disease, Chronic ObstructiveAgedBronchiCpG IslandsEpigenomicsFemaleGenome-Wide Association StudyHumansMaleMiddle AgedSeverity of Illness IndexSmokingAirway EpitheliumPulmonary Disease, Chronic Obstructive

Identifiers

PMID41419234
PMCPMC12716595

What Socratic holds

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Registered trials

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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.