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Prenatal Tobacco Smoke Exposure Is Associated with Childhood DNA CpG Methylation
Open accessAbstract
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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“smoking during pregnancy causes long-lasting changes in DNA methylation if offspring(213) that are observed in fetal lung,(214) cord blood,(214) and which continue to be present in the blood of school-age children.(215)”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [215]
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DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis
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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)
- 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
- gold
- doi.org
- 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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