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Cited by 122Epigenetics and DNA MethylationSmoking Behavior and CessationAsthma and respiratory diseases

The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.

Prenatal Tobacco Smoke Exposure Is Associated with Childhood DNA CpG Methylation

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Breton, Carrie V., Siegmund, Kimberly D., Joubert, Bonnie R., Wang, Xinhui, Qui, Weiliang, Carey, Vincent, Nystad, Wenche, Håberg, Siri E., Ober, Carole, Nicolae, Dan, Barnes, Kathleen C., Martinez, Fernando, Liu, Andy, Lemanske, Robert, Strunk, Robert, Weiss, Scott, London, Stephanie, Gilliland, Frank, Raby, Benjamin, on behalf of the Asthma BRIDGE consortium·2014·PLoS ONE
DOI 10.1371/journal.pone.0099716PMC PMC4070909
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Abstract

BACKGROUND: Smoking while pregnant is associated with a myriad of negative health outcomes in the child. Some of the detrimental effects may be due to epigenetic modifications, although few studies have investigated this hypothesis in detail. OBJECTIVES: To characterize site-specific epigenetic modifications conferred by prenatal smoking exposure within asthmatic children. METHODS: Using Illumina HumanMethylation27 microarrays, we estimated the degree of methylation at 27,578 distinct DNA sequences located primarily in gene promoters using whole blood DNA samples from the Childhood Asthma Management Program (CAMP) subset of Asthma BRIDGE childhood asthmatics (n = 527) ages 5-12 with prenatal smoking exposure data available. Using beta-regression, we screened loci for differential methylation related to prenatal smoke exposure, adjusting for gender, age and clinical site, and accounting for multiple comparisons by FDR. RESULTS: Of 27,578 loci evaluated, 22,131 (80%) passed quality control assessment and were analyzed. Sixty-five children (12%) had a history of prenatal smoke exposure. At an FDR of 0.05, we identified 19 CpG loci significantly associated with prenatal smoke, of which two replicated in two independent populations. Exposure was associated with a 2% increase in mean CpG methylation in FRMD4A (p = 0.01) and Cllorf52 (p = 0.001) compared to no exposure. Four additional genes, XPNPEP1, PPEF2, SMPD3 and CRYGN, were nominally associated in at least one replication group. CONCLUSIONS: These data suggest that prenatal exposure to tobacco smoke is associated with reproducible epigenetic changes that persist well into childhood. However, the biological significance of these altered loci remains unknown.

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Figure 1 Boxplots showing the distribution of % CpG methylation after normalization and batch correction using COMBAT by IUS exposure for A) C11orf52 (cg05697249), B) XPNPEP1 (cg09352789), C) FRMD4A (cg25464840), and D) PPEF2 (cg14724265) in 526 Asthma BRIDGE samples.
Figure 1 Boxplots showing the distribution of % CpG methylation after normalization and batch correction using COMBAT by IUS exposure for A) C11orf52 (cg05697249), B) XPNPEP1 (cg09352789), C) FRMD4A (cg25464840), and D) PPEF2 (cg14724265) in 526 Asthma BRIDGE samples.CC0 · PubMed Central

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Metadata

Authors
Breton, C. V., Siegmund, K. D., Joubert, B. R., Wang, X., Qui, W., Carey, V., Nystad, W., Håberg, S. E., Ober, C., Nicolae, D., Barnes, K. C., Martinez, F., Liu, A., Lemanske, R., Strunk, R., Weiss, S., London, S., Gilliland, F., Raby, B., & on behalf of the Asthma BRIDGE consortium
Affiliations
  • University of Southern California (US)
  • National Institutes of Health (US)
  • Brigham and Women's Hospital (US)
  • Norwegian Institute of Public Health (NO)
  • University of Chicago (US)
  • Johns Hopkins University (US)
  • National Jewish Health (US)
  • University of Wisconsin–Madison (US)
  • Washington University in St. Louis (US)
Corresponding author
Breton, Carrie V.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2014-06-25
Volume
9
Issue
6
Pages
e99716
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0099716
PMC
PMC4070909
OpenAlex
W2102688739
Cited by
119
References
47
Citations by year
2026: 3 · 2025: 1 · 2024: 1 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 8 · 2019: 16 · 2018: 14 · 2017: 18 · 2016: 14 · 2015: 22 · 2014: 8
FWCI
8.43
Type
journal article
Language
en
Update notices
correction (2014-10-28)
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, public-domain)
  • Europe PMC (PubMed Central) (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • Knowledge@UChicago (University of Chicago) (submittedVersion, cc-by-nc-nd)
  • BIBSYS Brage (BIBSYS (Norway)) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
  • University of Chicago
Funders
  • Brigham and Women's Hospital
  • Norges Forskningsråd (151918/S10)
  • National Institutes of Health (UL1TR000430, NO-ES-75558, n01es75558-11-0-1, HL65899, HL083069)
  • National Heart, Lung, and Blood Institute (U01HL065899, R01HL118455, HL075419, RC2HL101543, HL-65899, U01HL075419, R01HL086601, P01HL083069, HL083069)
  • National Institute of Allergy and Infectious Diseases (U19AI095230)
  • National Institute of Neurological Disorders and Stroke (1-UO1-NS-047537, UO1-NS-047537, 047537-01, UO1 NS 047537–01, NS 047537, U01NS047537, 1 UO1 NS 047537‐01)
  • National Institute of Environmental Health Sciences (ES-75558, UO1 NS 047537-01, NO-ES-75558, N01 ES075558, 1 UO1 NS 047537-01, N0-ES-75 558, K01ES017801, P30ES007048)
  • National Center for Advancing Translational Sciences
  • NHLBI Division of Intramural Research
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
Keywords
prenatal tobacco exposure, smoking during pregnancy, DNA methylation, CpG methylation, childhood asthma, epigenetic modifications, promoter, SMPD3, Childhood Asthma Management Program
MeSH terms
Asthma, Child, Child, Preschool, Female, Humans, Male, Pregnancy, Prenatal Exposure Delayed Effects, Smoking, CpG Islands, DNA Methylation, Epigenesis, Genetic

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