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DNA methylation links prenatal smoking exposure to later life health outcomes in offspring

DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
DNA methylation links prenatal smoking exposure to later life health outcomes in offspring
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 We identify 69 differentially methylated CpGs in 36 genomic regions (P value < 1 × 10−7) 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.
1868-7075
97
Wiklund, Petri
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Karhunen, Ville
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Richmond, Rebecca C.
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Parmar, Priyanka
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Rodriguez, Alina
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De Silva, Maneka
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Wielscher, Matthias
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Rezwan, Faisal I.
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Richardson, Tom G
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Veijola, Juha
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Herzig, Karl-Heinz
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Holloway, John W.
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Relton, Caroline L.
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Sebert, Sylvain
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Järvelin, Marjo-Riitta
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Wiklund, Petri
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Karhunen, Ville
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Richmond, Rebecca C.
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Parmar, Priyanka
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Rodriguez, Alina
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De Silva, Maneka
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Wielscher, Matthias
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Rezwan, Faisal I.
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Richardson, Tom G
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Veijola, Juha
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Herzig, Karl-Heinz
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Holloway, John W.
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Relton, Caroline L.
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Sebert, Sylvain
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Järvelin, Marjo-Riitta
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Wiklund, Petri, Karhunen, Ville, Richmond, Rebecca C., Parmar, Priyanka, Rodriguez, Alina, De Silva, Maneka, Wielscher, Matthias, Rezwan, Faisal I., Richardson, Tom G, Veijola, Juha, Herzig, Karl-Heinz, Holloway, John W., Relton, Caroline L., Sebert, Sylvain and Järvelin, Marjo-Riitta (2019) DNA methylation links prenatal smoking exposure to later life health outcomes in offspring. Clinical Epigenetics, 11 (1), 97. (doi:10.1186/s13148-019-0683-4).

Record type: Article

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 We identify 69 differentially methylated CpGs in 36 genomic regions (P value < 1 × 10−7) 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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Accepted/In Press date: 13 May 2019
Published date: 1 July 2019

Identifiers

Local EPrints ID: 431487
URI: http://eprints.soton.ac.uk/id/eprint/431487
ISSN: 1868-7075
PURE UUID: d04a7565-9b52-4c09-8126-3c0515f49657
ORCID for Faisal I. Rezwan: ORCID iD orcid.org/0000-0001-9921-222X
ORCID for John W. Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 05 Jun 2019 16:30
Last modified: 10 Jan 2022 05:44

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Contributors

Author: Petri Wiklund
Author: Ville Karhunen
Author: Rebecca C. Richmond
Author: Priyanka Parmar
Author: Alina Rodriguez
Author: Maneka De Silva
Author: Matthias Wielscher
Author: Faisal I. Rezwan ORCID iD
Author: Tom G Richardson
Author: Juha Veijola
Author: Karl-Heinz Herzig
Author: Caroline L. Relton
Author: Sylvain Sebert
Author: Marjo-Riitta Järvelin

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