Fig. 3
Enriched regulatory elements and pathways of smoking-associated CpGs (smCpGs). A cell-type-specific regulatory components. B canonical pathways of the genes annotated to smCpGs in each blood cell type. The color gradient indicts the significance (− Log10p value) and the size of dots indicts the number of genes involved. Detailed pathways and involved genes for B cell smCpGs are listed in Additional file 7: Table S6. *Indicates pathways of differentially methylated region-annotated genes involved in naïve-to-memory B cell differentiation. C Volcano plot of differentially expressed genes (DEGs) in B cells depicts negative Log10-transformed p values against Log2-transformed fold changes of DEGs in smoker B cells at different significance levels. Open circles indicate DEGs involved in naive B cell activation to be differentiated into memory cells. D Dot plot depicts the enriched pathways of blood B cell transcriptomics in smokers (n = 519 at p < 0.01), those remaining after adjustment (n = 419, p < 0.01) and those involved in naïve-to-memory B cell differentiation in smokers (n = 313, p < 0.01). Differentially expressed genes (DEGs) determined by RNA sequencing analysis (RNA-seq) with adjustment for nine covariates (age, sex, race, body mass index, CD4T %, CD8T %, NK %, Monocyte %, Granulocyte %) or ten (9 covariates + Naïve B cell %). Selected top-ranked canonical pathways are identified by IPA. Dot size indicts the –Log10 adjusted p values of the pathways. Dot color presents activation z-score trend. Detailed pathways and involved genes listed in Table S10. E Common 36 genes between RNA-seq (p < 0.01) and epigenome-wide association study (false discovery rate 1%) analyses of B cells in smokers