Additional file 3 of In utero and childhood exposure to tobacco smoke and multi-layer molecular signatures in children

Additional file 3: Additional Fig. S1-S5 and Fig. S7-S15. Fig. S1. Directed acyclic graph (DAG) with causal assumptions from a priori knowledge between maternal smoking during pregnancy (MSDP) and child molecular features. In blue, the causal path assessed in the model. Fig. S2. Directed acyclic graph (DAG) with causal assumptions from a priori knowledge between childhood SHS and child molecular features. Fig. S3. Percentage of children exposed to tobacco smoking in the study population and by cohort: any (A) and sustained (B) maternal smoking during pregnancy (MSDP), childhood global-SHS (C), and child urinary cotinine measurements (D). Fig. S4. QQ-plot and Volcano-plot of the associations between child DNA methylation and any (A and B) and sustained (C and D) maternal smoking during pregnancy (MSDP), adjusted for global-SHS. Fig. S5. Comparison of effects on child blood DNA methylation between any and sustained maternal smoking during pregnancy (MSDP), adjusted for global-SHS. Fig. S7. Plot showing significance of methylation to expression relationships (−log10(p-value)) in relation to the distance between TC-TSS and CpG. Fig. S8. QQ-plot of the associations between child blood gene expression and global-SHS (A) and urinary cotinine (B), adjusted for sustained maternal smoking during pregnancy (MSDP), among 1270 genes identified in current smokers at 10% FDR (Huan et al. 2016). Fig. S9. QQ-plot of the associations between child blood DNA methylation and global-SHS (A) and urinary cotinine (B), adjusted for sustained maternal smoking during pregnancy (MSDP), among 18,763 CpGs identified in current smoking at 5% FDR (Joehanes et al. 2016). Fig. S10. QQ-plot of the associations between child blood DNA methylation and any (A) and sustained (B) maternal smoking during pregnancy (MSDP), adjusted for global-SHS, among 18,763 CpGs identified in current smoking at 5% FDR (Joehanes et al. 2016). Fig. S11. Interaction between any maternal smoking during pregnancy (MSDP) and global-SHS. The y-axis shows predicted methylation levels at cg01664727 (at RUNX1 locus). Fig. S12. Comparison of effects of maternal smoking during pregnancy (MSDP) on child blood DNA methylation between models adjusted for global-SHS and for home-SHS. Fig. S13. Comparison of effects of maternal smoking during pregnancy (MSDP) on child blood DNA methylation between models adjusted for global-SHS and unadjusted model. Fig. S14. Comparison of effects of maternal smoking during pregnancy (MSDP) on child blood DNA methylation between datasets including all children and including only European ancestry children. Fig. S15. Schematic representation of PAI1 cascade. In red inhibition steps and in green activation steps.