Figures and data
Characteristics of the epigenetic subsample (1,267 mother–newborn pairs) from the CHILD, FAMILY, START.
* comparison for CHILD and FAMILY only
Schematic overview of the analytical pipeline for the cord blood DNAm maternal smoking score and association study.
Figure 1-A) shows the epigenome-wide association studies conducted in the European cohorts (CHILD and FAMILY); Figure 1-B) illustrated the workflow for methylation risk score (MRS) construction using an external EWAS (Joubert et al., 2016) as the discovery sample and CHILD study as the external validation study, while Figure 1-C) demonstrates the evaluation of the MRS in two independent cohorts of white European (i.e. FAMILY) and South Asian (i.e. START). The validated MRS was then tested for association with smoking specific, maternal, and children phenotypes in CHILD, FAMILY, and START, as shown in Figure 1-D).
* indicates cohort sample size including those with missing smoking history.
Manhattan plots of the meta-analyzed association between cord blood DNAm and maternal smoking in Europeans.
Manhattan plots summarized the meta-analyzed association p-values between cord blood DNA methylation levels and current maternal smoking (A) or smoking exposure (B) at a common set of 2,114 CpG sites. The red line denotes the smallest -log10(p-value) that is below the FDR correction threshold of 0.05. The red dots represent established associations with maternal smoking reported in Joubert and colleagues (19).
Meta-analysis results of association between CpGs and maternal smoking and smoking exposure that passed a marginal p < 0.05 threshold after the false discovery rate correction in European cohorts.
BMI: body mass index, T2D: type 2 diabetes, A: age, BW: birth weight
Relationships between maternal smoking MRS and maternal smoking history categories for each of the studies.
Maternal smoking methylation score (y-axis) was shown as a function of maternal smoking history (x-axis) in levels of severity for prenatal exposure for CHILD (A), FAMILY (B), and START (C). Each severity level was compared to the never-smoking group and the corresponding two-sample t-test p-value was reported. The analysis of variance via an F-test p-value was used to indicate whether a mean difference in methylation score was present among all smoking history categories. The sample size for START cohort was provided due to the low counts in categories of any smoking. The area under the receiver operating characteristic curve (AUC) for each study was shown in the lower panel.
