Cited by 188Epigenetics and DNA MethylationSmoking Behavior and CessationBirth, Development, and Health

Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age

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Lee, Ken W.K., Richmond, Rebecca, Hu, Pingzhao, French, Leon, Shin, Jean, Bourdon, Celine, Reischl, Eva, Waldenberger, Melanie +11 more·2015·Environmental Health Perspectives

Abstract

Abstract Background: Prenatal exposure to maternal cigarette smoking (prenatal smoke exposure) had been associated with altered DNA methylation (DNAm) at birth. Objective: We examined whether such alterations are present from birth through adolescence. Methods: We used the Infinium HumanMethylation450K BeadChip to search across 473,395 CpGs for differential DNAm associated with prenatal smoke exposure during adolescence in a discovery cohort (n = 132) and at birth, during childhood, and during adolescence in a replication cohort (n = 447). Results: In the discovery cohort, we found five CpGs in MYO1G (top-ranking CpG: cg12803068, p = 3.3 × 10–11) and CNTNAP2 (cg25949550, p = 4.0 × 10–9) to be differentially methylated between exposed and nonexposed individuals during adolescence. The CpGs in MYO1G and CNTNAP2 were associated, respectively, with higher and lower DNAm in exposed versus nonexposed adolescents. The same CpGs were differentially methylated at birth, during childhood, and during adolescence in the replication cohort. In both cohorts and at all developmental time points, the differential DNAm was in the same direction and of a similar magnitude, and was not altered appreciably by adjustment for current smoking by the participants or their parents. In addition, four of the five EWAS (epigenome-wide association study)–significant CpGs in the adolescent discovery cohort were also among the top sites of differential methylation in a previous birth cohort, and differential methylation of CpGs in CYP1A1, AHRR, and GFI1 observed in that study was also evident in our discovery cohort. Conclusions: Our findings suggest that modifications of DNAm associated with prenatal maternal smoking may persist in exposed offspring for many years—at least until adolescence. Citation: Lee KW, Richmond R, Hu P, French L, Shin J, Bourdon C, Reischl E, Waldenberger M, Zeilinger S, Gaunt T, McArdle W, Ring S, Woodward G, Bouchard L, Gaudet D, Davey Smith G, Relton C, Paus T, Pausova Z. 2015. Prenatal exposure to maternal cigarette smoking and DNA methylation: epigenome-wide association in a discovery sample of adolescents and replication in an independent cohort at birth through 17 years of age. Environ Health Perspect 123:193–199; http://dx.doi.org/10.1289/ehp.1408614

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  • Meta-analysis of blood from human newborn infants born of mothers who smoked during pregnancy found differentially methylated CpGs associated with gene expression in pathways and processes critical to development.

    “Meta-analysis of blood from human newborn infants born of mothers who smoked during pregnancy found differentially methylated CpGs associated with gene expression in pathways and processes critical to development [177,178].”

    From Nicotine on the developing brain. (2023) · cites this paper as [177]

    The Results (page not provided) report differentially methylated CpGs in newborns exposed to maternal smoking, but the study is an adolescent discovery analysis with newborn replication, not a meta-analysis of newborn blood. The Discussion (page not provided) says the CpGs might alter gene expression and explicitly states that this remains to be studied; it does not establish gene-expression associations across developmental pathways. (LLM, conf=0.88)

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Authors
Lee, K. W. K., Richmond, R., Hu, P., French, L., Shin, J., Bourdon, C., Reischl, E., Waldenberger, M., Zeilinger, S., Gaunt, T., McArdle, W., Ring, S., Woodward, G., Bouchard, L., Gaudet, D., Smith, G. D., Relton, C., Paus, T., & Pausova, Z.
Affiliations
  • University of Toronto (CA)
  • University of Bristol (GB)
  • The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  • Helmholtz Munich (DE)
  • Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, Munich, Germany
  • Norwegian University of Science and Technology (NO)
  • Université de Sherbrooke (CA)
  • Hôpital de Chicoutimi (CA)
  • Rotman Research Institute, University of Toronto, Toronto, Ontario, Canada
Venue
Environmental Health Perspectives
Published
2014-10-17
Volume
123
Issue
2
Pages
193-199
ISSN
  • 0091-6765 (ISSN-L)
  • 1552-9924
OpenAlex
W1972219651
Cited by
186
References
49
Citations by year
2026: 3 · 2025: 8 · 2024: 5 · 2023: 15 · 2022: 15 · 2021: 13 · 2020: 17 · 2019: 20 · 2018: 21 · 2017: 21 · 2016: 30 · 2015: 16 · 2014: 2
FWCI
9.44
Type
journal article
Language
en
Open access
Locations
  • Environmental Health Perspectives (publishedVersion, public-domain)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Explore Bristol Research (publishedVersion)
  • Site cant be reached (submittedVersion)
  • Bristol Research (University of Bristol) (submittedVersion)
  • Newcastle University ePrints (Newcastle Univesity)
Funders
  • Wellcome Trust (102215, 092731)
  • Canadian Institutes of Health Research
  • Medical Research Council (MC_PC_15018)
  • Biotechnology and Biological Sciences Research Council (BB/I025263/1, BB/I025751/1)
  • Economic and Social Research Council (ES/L003023/1)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
maternal cigarette smoking, prenatal tobacco exposure, DNA methylation, epigenome-wide association study, CNTNAP2, CYP1A1, AHRR, GFI1, adolescent development, childhood, birth cohort, transgenerational epigenetic effects, smoking during pregnancy, CpG sites, offspring outcomes
MeSH terms
Adolescent, Adult, Child, England, Female, Humans, Infant, Newborn, Male, Pregnancy, Prenatal Exposure Delayed Effects, Quebec, Smoking, Cohort Studies, Maternal Exposure, DNA Methylation, Epigenesis, Genetic, Genome-Wide Association Study

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