Evidence map›Paper›PMID 23065012›Full record

ArticleAmerican journal of respiratory and critical care medicine2012

Systemic steroid exposure is associated with differential methylation in chronic obstructive pulmonary disease.

Emily S Wan, Weiliang Qiu, Andrea Baccarelli, Vincent J Carey, Helene Bacherman, Stephen I Rennard, Alvar Agustí, Wayne H Anderson, David A Lomas, Dawn L DeMeo

Abstract read
In one paragraph

Article in American journal of respiratory and critical care medicine, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.9field-weighted citation impact, top 7% of its field
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

41 citing papers in PubMed, 87 citations in OpenAlex.

  1. DNA methylation is associated with inhaled corticosteroid response in persistent childhood asthmatics.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2019
    Trial
  2. Reduced Methylation of IRF5 Gene as a Biomarker for Gestational Diabetes Mellitus.Medical science monitor : international medical journal of experimental and clinical research · 2025
    Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Epigenetic Mechanisms Modulated by Glucocorticoids With a Focus on Cushing Syndrome.The Journal of clinical endocrinology and metabolism · 2024
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Role of inflammasome in severe, steroid-resistant asthma.Current research in immunology · 2023
    Review
  13. Article
  14. Article
  15. Article
  16. The apolipoprotein receptor LRP3 compromises APP levels.Alzheimer's research & therapy · 2021
    Article
  17. Review
  18. Article
  19. Article
  20. 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

10 authors at 6 institutions in 3 countries.

Emily S WanChanning Division of Network Medicine, Brigham and Women’s Hospital, Boston, Massachusetts, USA. reesw@channing.harvard.edu
Weiliang Qiu
Andrea Baccarelli
Vincent J Carey
Helene Bacherman
Stephen I Rennard
Alvar Agustí
Wayne H Anderson
David A Lomas
Dawn L DeMeo
Brigham and Women's Hospital · USCentro de Investigación Biomédica en Red de Enfermedades Respiratorias · ESHarvard University · USUniversity of Cambridge · GBUniversity of Nebraska Medical Center · USUniversity of North Carolina at Chapel Hill · US

Funding

Translational Research Support CoreP30ES000002 · NIEHS · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI JAIME ELIZABETH HART · 1985 to 2026
$44.6M
SYSTEMS APPROACHES TO THE EPIDEMIOLOGY, GENETICS AND GENOMICS OF LUNG DISEASEST32HL007427 · NHLBI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI DAWN L DEMEO, Edwin K Silverman · 1985 to 2026
$13.6M
Genetic Features of Gender Differences in COPDR01HL089438 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI DEMEO, DAWN L · 2008 to 2011
$3.3M
Translational Genetics and Genomics of Airways DiseasesK12HL089990 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI WEISS, SCOTT T · 2007 to 2012
$1.9M
Medical Research Council G0901786NHLBI NIH HHS K12 HL089990NHLBI NIH HHS K12HL089990NHLBI NIH HHS R01 HL089438NHLBI NIH HHS R01HL089438NHLBI NIH HHS T32 HL007427NIEHS NIH HHS ES00002NIEHS NIH HHS P30 ES000002
6 · The paper itself

Abstract

rationaleSystemic glucocorticoids are used therapeutically to treat a variety of medical conditions. Epigenetic processes such as DNA methylation may reflect exposure to glucocorticoids and may be involved in mediating the responses and side effects associated with these medications.

objectivesTo test the hypothesis that differences in DNA methylation are associated with current systemic steroid use.

methodsWe obtained DNA methylation data at 27,578 CpG sites in 14,475 genes throughout the genome in two large, independent cohorts: the International COPD Genetics Network (n(discovery) = 1,085) and the Boston Early Onset COPD study (n(replication) = 369). Sites were tested for association with current systemic steroid use using generalized linear mixed models. MEASUREMENTS AND MAIN

resultsA total of 511 sites demonstrated significant differential methylation by systemic corticosteroid use in all three of our primary models. Pyrosequencing validation confirmed robust differential methylation at CpG sites annotated to genes such as SLC22A18, LRP3, HIPK3, SCNN1A, FXYD1, IRF7, AZU1, SIT1, GPR97, ABHD16B, and RABGEF1. Functional annotation clustering demonstrated significant enrichment in intrinsic membrane components, hemostasis and coagulation, cellular ion homeostasis, leukocyte and lymphocyte activation and chemotaxis, protein transport, and responses to nutrients.

conclusionsOur analyses suggest that systemic steroid use is associated with site-specific differential methylation throughout the genome. Differentially methylated CpG sites were found in biologically plausible and previously unsuspected pathways; these genes and pathways may be relevant in the development of novel targeted therapies.

Indexed as

CpG IslandsDNA MethylationEpigenesis, GeneticFamilyFemaleForced Expiratory VolumeGenome, HumanGlucocorticoidsHumansMaleMiddle AgedPulmonary Disease, Chronic ObstructiveSmokingVital CapacityGlucocorticoids

Identifiers

PMID23065012
PMCPMC3622442
OpenAlexW1985895058

What OpenQuestion holds

Textmetadata
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.