Maternal cigarette smoking during pregnancy and offspring DNA methylation in midlife

Tehranifar, Parisa; Wu, Hui‐Chen; McDonald, Jasmine A.; Jasmine, Farzana; Santella, Regina M.; Gurvich, Irina; Flom, Julie D.; Terry, Mary Beth

doi:10.1080/15592294.2017.1325065

Cited by 50 publications

(59 citation statements)

References 38 publications

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“…Findings are also consistent with a recent report that highlighted persistence of DNA methylation levels related to prenatal smoke exposure into adulthood, 17 which identified associations the same CpG sites located in MYO1G and CYP1A1 , and other CpG sites in FTO and AHRR .…”

Section: Discussionsupporting

confidence: 92%

DNA methylation as a marker for prenatal smoke exposure in adults

Richmond

Suderman

Langdon

et al. 2018

International Journal of Epidemiology

105

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BackgroundPrenatal smoke exposure is known to be robustly associated with DNA methylation among offspring in early life, but whether the association persists into adulthood is unclear. This study aimed to investigate the long-term effect of maternal smoke exposure on DNA methylation in 754 women (mean age 30 years); to replicate findings in the same women 18 years later and in a cohort of 230 men (mean age 53 years); and to assess the extent to which a methylation score could predict prenatal smoke exposure.MethodsWe first carried out an epigenome-wide association analysis for prenatal smoke exposure and performed replication analyses for the top CpG sites in the other samples. We derived a DNA methylation score based on previously identified CpG sites and generated receiver operating characteristic (ROC) curves to assess the performance of these scores as predictors of prenatal smoke exposure.ResultsWe observed associations at 15 CpG sites in 11 gene regions: MYO1G, FRMD4A, CYP1A1, CNTNAP2, ARL4C, AHRR, TIFAB, MDM4, AX748264, DRD1, FTO (false discovery rate <5%). Most of these associations were specific to exposure during pregnancy, were present 18 years later and were replicated in a cohort of men. A DNA methylation score could predict prenatal smoke exposure (30 years previously) with an area under the curve of 0.72 (95% confidence interval 0.69, 0.76).ConclusionsThe results of this study provide robust evidence that maternal smoking in pregnancy is associated with changes in DNA methylation that persist in the exposed offspring for many years after prenatal exposure.

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Section: Discussionsupporting

confidence: 92%

DNA methylation as a marker for prenatal smoke exposure in adults

Richmond

Suderman

Langdon

et al. 2018

International Journal of Epidemiology

105

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“…The longitudinal analysis showed that differentially methylated CpGs observed around age 30 persisted into middle age (around age 48) without significant change in direction or magnitude of methylation levels. This corroborates the findings of recent smaller studies, which found several differently methylated CpGs in middle-aged women exposed to maternal smoking in utero 14,15 and suggests that some of the prenatal smoking exposure associated methylation changes are largely irreversible and unaffected by age and/or environmental exposures later in life. To assess whether such persistent changes in DNA methylation are causally implicated with disease, we performed a Mendelian randomization analysis using summary data from large epigenome-wide association studies 24 .…”

Section: Discussionsupporting

confidence: 90%

“…In support of this, an epigenome-wide meta-analysis of 13 birth cohort studies identified over 6,000 differentially methylated CpGs in cord blood of newborns exposed to prenatal smoking 11 . Several smaller studies have suggested that some of these methylation changes may persist across childhood and adolescence 12,13 into adulthood 14,15 . However, questions remain concerning whether such DNA methylation changes endure across the life course and whether they play a mediating role in linking prenatal smoke exposure to later life health outcomes.…”

Section: Introductionmentioning

confidence: 99%

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

Wiklund

Karhunen

Richmond

et al. 2018

Preprint

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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. To test this, we examined the association of prenatal maternal smoking with DNA methylation in 2,821 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. We identify 69 differentially methylated CpGs in 36 genomic regions (P < 1×10 -7 ), and show that 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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“…Importantly, in this study, we identified six novel sites, which were replicated across tissues, using the 850k newer chip design. Several well-documented findings were replicated in this study, including DNAm of the AHRR gene on chromosome 5, which has previously been associated with both adult and maternal smoking [14][15][16][17]. The aryl-hydrocarbon receptor (AhR) pathway and the methylation of the related AHRR gene has been proposed as a potential biomarker of cardiovascular disease, specifically atherosclerosis, in smokers [9].…”

Section: Discussionsupporting

confidence: 67%