Abstract
Maternal smoking and micronutrient intake during pregnancy are two strong biological candidates for impacting the developing epigenome. The extent to which DNA methylation in offspring is modified by these intrauterine exposures has not been presented in parallel. In this review, we summarize human studies which have investigated genome-wide DNA methylation in the offspring in relation to maternal smoking and one-carbon micronutrient exposure during pregnancy. We contrast the primarily independent efforts for these two categories of exposure, and potential explanations for these differences. We emphasize methodological considerations such as power to detect methylation signals, exposure assessment, control of sources of variability, causal inference and the role of observed methylation changes in mediating downstream outcomes in the offspring.
Highlights
Describes in detail the profound effect of smoke exposure on DNA methylation profiles which have been identified in response to both personal smoking and perinatal exposur
An amassing number of epigenome-wide association studies (EWAS) for maternal smoking has led to the identification of a plethora of strong, highly replicated methylation signatures
Stronger statistical significance was observed for the maternal smoking studies compared with the micronutrient studies, and methylation sites were more consistently replicated between studies
Summary
We review two categories of exposures Cigarette smoke, as well as being a known that have been considered strong biologi- carcinogen which has detrimental health cal candidates for impacting the developing consequences for smokers, is a well-estabepigenome: maternal smoking during preg- lished toxicant associated with many health nancy and maternal one-carbon micronutri- effects in the offspring of those exposed ent exposures during pregnancy. Because of the relevance to early life health outcomes such as neural tube defects, some studies such as Price et al [78] have evaluated the relationship between folate levels and neural tube defects to consider mediating effects of methylation Despite these findings it remains to be seen whether the small observed changes in DNA methylation are biologically (e.g., impacting transcription) or clinically relevant and whether the association with offspring phenotypes are truly causal. Attempts should be made to investigate concordance of methylation signatures between tissues in relation to a maternal exposure, which can provide more insight into systemic effects, and to investigate mediation of methylation in target tissues more closely linked with the offspring outcomes of interest rather than peripheral tissues [12]
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