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

Rodriguez, Alina and Karhunen, Ville and Richmond, Rebecca and Rodriguez, Alina and De Silva, Maneka and Wielscher, Matthias and Rezwan, Faisal and Richardson, Tom and Veijola, Juha and Heinz-Herzig, Karl and Holloway, John and Relton, Caroline and Sebert, Sylvain and Järvelin, Marjo-Riitta (2019) DNA methylation links prenatal smoking exposure to later life health outcomes in offspring. Clinical Epigenetics, 11 (1). ISSN 1868-7075

Full content URL: https://doi.org/10.1186/s13148-019-0683-4

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Abstract

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 diseases 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.

Keywords:Maternal smoking, Pregnancy, DNA methylation, Persistence, Mediation, Disease, Causality, Life course
Subjects:C Biological Sciences > C840 Clinical Psychology
C Biological Sciences > C420 Human Genetics
C Biological Sciences > C431 Medical Genetics
C Biological Sciences > C860 Neuropsychology
C Biological Sciences > C440 Molecular Genetics
Divisions:College of Social Science > School of Psychology
ID Code:36260
Deposited On:21 Jun 2019 10:53

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