Dataset Information

DNA methylation as a marker for prenatal smoke exposure in adults.

ABSTRACT:

Background

Prenatal 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.

Methods

We 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.

Results

We 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).

Conclusions

The 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.

SUBMITTER: Richmond RC

PROVIDER: S-EPMC6124615 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Publications

DNA methylation as a marker for prenatal smoke exposure in adults.

Richmond Rebecca C RC Suderman Matthew M Langdon Ryan R Relton Caroline L CL Davey Smith George G

International journal of epidemiology 20180801 4

<h4>Background</h4>Prenatal 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 pr ...[more]

PMID: 29860346

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Project description:IntroductionFetal changes in DNA methylation may underlie associations of maternal smoking during pregnancy with adverse outcomes in children. We examined critical periods and doses of maternal smoking during pregnancy in relation to newborn DNA methylation, and associations of paternal smoking with newborn DNA methylation.Aims and methodsThis study was embedded in the Generation R Study, a population-based prospective cohort study from early pregnancy onwards. We assessed parental smoking during pregnancy using questionnaires. We analyzed associations of prenatal smoke exposure with newborn DNA methylation at 5915 known maternal smoking-related cytosine-phosphate-guanine sites (CpGs) in 1261 newborns using linear regression. Associations with false discovery rate-corrected p-values < .05 were taken forward.ResultsSustained maternal smoking was associated with newborn DNA methylation at 1391 CpGs, compared with never smoking. Neither quitting smoking early in pregnancy nor former smoking was associated with DNA methylation, compared with never smoking. Among sustained smokers, smoking ≥5, compared with <5, cigarettes/d was associated with DNA methylation at seven CpGs. Paternal smoking was not associated with DNA methylation, independent of maternal smoking status.ConclusionsOur results suggest that CpGs associated with sustained maternal smoking are not associated with maternal smoking earlier in pregnancy or with paternal smoking. Some of these CpGs show dose-response relationships with sustained maternal smoking. The third trimester may comprise a critical period for associations of smoking with newborn DNA methylation, or sustained smoking may reflect higher cumulative doses. Alternatively, maternal smoking limited to early pregnancy and paternal smoking may be associated with DNA methylation at specific other CpGs not studied here.ImplicationsOur results suggest that quitting maternal smoking before the third trimester of pregnancy, and possibly lowering smoking dose, may prevent differential DNA methylation in the newborns at CpGs associated with sustained smoking. If the relevance of DNA methylation for clinical outcomes is established, these results may help in counseling parents-to-be about quitting smoking.

Project description:Background: How prenatal smoke exposure affects DNA methylation leading to atopic disorders remains to be addressed. Epigenetic biomarkers informative of prenatal smoke exposure and atopic disorders are wanting. Since most children suffering from atopic dermatitis (AD) continue to develop asthma later in life, we explored whether prenatal smoke exposure e induces DNA methylation and searched for predictive epigenetic biomarkers for smoke related atopic disorders. Methods: Methylation differences associated with smoke exposure were screened by Illumina methylation panel for children from the Taiwan birth panel study cohort initially. Information about development of atopic dermatitis (AD) and risk factors were collected. Cord blood cotinine levels were measured to represent prenatal smoke exposure. CpG loci that demonstrated a statistically significant difference in methylation were validated by methylation-dependent fragment separation (MDFS). Differential methylation in three genes (TSLP, GSTT1, and CYB5R3) was identified through the screen and their functions were investigated. Results: Among these, only thymic stromal lymphopoietin (TSLP) gene displayed significant difference in promoter methylation percentage after being validated by MDFS (p=0.029). TSLP gene was further investigated in a larger sample of 92 children from the cohort. Methylation status of the TSLP 5′-CpG island (CGI) was found to be significantly associated with prenatal smoke exposure (OR=3.59, 95%CI=1.49-8.64; cotinine level 0.10 ng/ml, sensitivity= 77%; specificity = 61%) and with AD (OR=4.77, 95%CI=1.47-15.53). The degree of TSLP 5′CGI methylation inversely correlated with TSLP protein expression levels (per unit: β=－6.69 ng/ml; 95% CIs, －12.80~－0.59; p=0.032). Conclusions: The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation. Cord blood methylated TSLP 5′CGI may be a potential epigenetic biomarker for environmentally-related atopic disorders. The buffy coat and plasma samples were separated and stored at −80°C. DNA (100 ng-500 ng) was extracted from cord white blood cells. Microarrays have been performed to investigate fourteen samples, which were classified as two groups according to cotinine exposure dosage (7 versus 7 : high exposure verses low exposure).

Project description:Exposure to phthalates has been shown to impede the human endocrine system, resulting in deleterious effects on pregnant women and their children. Phthalates modify DNA methylation patterns in infant cord blood. We examined the association between prenatal phthalate exposure and DNA methylation patterns in cord blood in a Korean birth cohort. Phthalate levels were measured in 274 maternal urine samples obtained during late pregnancy and 102 neonatal urine samples obtained at birth, and DNA methylation levels were measured in cord blood samples. For each infant in the cohort, associations between CpG methylation and both maternal and neonate phthalate levels were analyzed using linear mixed models. The results were combined with those from a meta-analysis of the levels of phthalates in maternal and neonatal urine samples, which were also analyzed for MEOHP, MEHHP, MnBP, and DEHP. This meta-analysis revealed significant associations between the methylation levels of CpG sites near the CHN2 and CUL3 genes, which were also associated with MEOHP and MnBP in neonatal urine. When the data were stratified by the sex of the infant, MnBP concentration was found to be associated with one CpG site near the OR2A2 and MEGF11 genes in female infants. In contrast, the concentrations of the three maternal phthalates showed no significant association with CpG site methylation. Furthermore, the data identified distinct differentially methylated regions in maternal and neonatal urine samples following exposure to phthalates. The CpGs with methylation levels that were positively associated with phthalate levels (particularly MEOHP and MnBP) were found to be enriched genes and related pathways. These results indicate that prenatal phthalate exposure is significantly associated with DNA methylation at multiple CpG sites. These alterations in DNA methylation may serve as biomarkers of maternal exposure to phthalates in infants and are potential candidates for investigating the mechanisms by which phthalates impact maternal and neonatal health.

Dataset Information

DNA methylation as a marker for prenatal smoke exposure in adults.

Background

Methods

Results

Conclusions

Publications

DNA methylation as a marker for prenatal smoke exposure in adults.

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