DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
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Abstract
BACKGROUND: Maternal smoking during pregnancy is associated with adverse offspring health outcomes across their life course. We hypothesize that DNA methylation is a potential mediator of this relationship. METHODS: We examined the association of prenatal maternal smoking with offspring blood DNA methylation in 2821 individuals (age 16 to 48 years) from five prospective birth cohort studies and perform Mendelian randomization and mediation analyses to assess whether methylation markers have causal effects on disease outcomes in the offspring. RESULTS: ) associated with exposure to maternal smoking in adolescents and adults. Mendelian randomization analyses provided evidence for a causal role of four maternal smoking-related CpG sites on an increased risk of inflammatory bowel disease or schizophrenia. Further mediation analyses showed some evidence of cg25189904 in GNG12 gene mediating the effect of exposure to maternal smoking on schizophrenia-related outcomes. CONCLUSIONS: DNA methylation may represent a biological mechanism through which maternal smoking is associated with increased risk of psychiatric morbidity in the exposed offspring.
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Further analysis provided evidence for a causal role of four maternal smoking related CpG sites in increasing the risk of schizophrenia and inflammatory bowel disease.
“Further analysis provided evidence for a causal role of four maternal smoking related CpG sites in increasing the risk of schizophrenia and inflammatory bowel disease [96].”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [96]
Combining data from five prospective birth cohort studies, researchers identified 69 differentially methylated CpGs in 36 genomic regions in offspring exposed to maternal smoking.
“Combing data from five prospective birth cohort studies, the researchers investigated the association between prenatal smoking exposure and offspring blood DNA methylation in 2821 adolescents and adults and identified 69 differentially methylated CpGs in 36 genomic regions of those exposed to maternal smoking.”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [96]
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- Authors
- Wiklund, P., Karhunen, V., Richmond, R. C., Parmar, P., Rodriguez, A., De Silva, M., Wielscher, M., Rezwan, F. I., Richardson, T. G., Veijola, J., Herzig, K.-H., Holloway, J. W., Relton, C. L., Sebert, S., & Järvelin, M.-R.
- Affiliations
- Imperial College London (GB)
- University of Bristol (GB)
- University of Oulu (FI)
- University of Southampton (GB)
- Oulu University Hospital (FI)
- Poznan University of Medical Sciences (PL)
- Corresponding author
- Järvelin, Marjo-Riitta
- ORCID
- Venue
- Clinical Epigenetics
- Published
- 2019-07-01
- Volume
- 11
- Issue
- 1
- Pages
- 97-97
- ISSN
- 1868-7075 (ISSN-L)
- 1868-7083
- PMC
- PMC6604191
- OpenAlex
- W2951038195
- Cited by
- 120
- References
- 53
- Citations by year
- 2026: 3 · 2025: 13 · 2024: 14 · 2023: 25 · 2022: 24 · 2021: 29 · 2020: 10 · 2019: 2
- FWCI
- 5.38
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Clinical Epigenetics (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion, cc-by)
- Lincoln Repository (University of Lincoln) (acceptedVersion)
- Jyväskylä University Digital Archive (University of Jyväskylä) (submittedVersion, cc-by)
- ePrints Soton (University of Southampton) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Explore Bristol Research (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion, cc-by)
- Funders
- H2020 European Institute of Innovation and Technology (633595)
- 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
- smoking during pregnancy, prenatal smoking exposure, DNA methylation, epigenetic mediation, inflammatory bowel disease, schizophrenia, psychiatric morbidity, CpG sites, offspring outcomes, birth cohort studies
- MeSH terms
- Adolescent, Adult, Female, Humans, Longitudinal Studies, Middle Aged, Pregnancy, Prenatal Exposure Delayed Effects, Prospective Studies, Schizophrenia, Smoking, Cohort Studies, Maternal Exposure, CpG Islands, DNA Methylation, Epigenesis, Genetic, GTP-Binding Protein gamma Subunits, Genome-Wide Association Study, Young Adult, Mendelian Randomization Analysis
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