Highly reproducible smoking-associated DNA methylation changes in whole blood have been reported by many Epigenome-Wide-Association Studies (EWAS). These epigenetic alterations could have important implications for understanding and predicting the risk of smoking-related diseases. To this end, it is important to establish if these DNA methylation changes happen in all blood cell subtypes or if they are cell-type specific. Here, we apply a cell-type deconvolution algorithm to identify cell-type specific DNA methylation signals in seven large EWAS. We find that most of the highly reproducible smoking-associated hypomethylation signatures are more prominent in the myeloid lineage. A meta-analysis further identifies a myeloid-specific smoking-associated hypermethylation signature enriched for DNase Hypersensitive Sites in acute myeloid leukemia. These results may guide the design of future smoking EWAS and have important implications for our understanding of how smoking affects immune-cell subtypes and how this may influence the risk of smoking related diseases.

许多表观基因组关联研究 (EWAS) 已经报告了全血中与吸烟相关的 DNA 甲基化变化的高度可重复性。这些表观遗传改变可能对理解和预测吸烟相关疾病的风险具有重要意义。为此，重要的是要确定这些 DNA 甲基化变化是否发生在所有血细胞亚型中，或者它们是否具有细胞类型特异性。在这里，我们应用细胞类型去卷积算法来识别七个大型 EWAS 中的细胞类型特异性 DNA 甲基化信号。我们发现大多数高度可重复的吸烟相关低甲基化特征在髓系谱系中更为突出。一项荟萃分析进一步确定了急性髓系白血病中富含 DNase 过敏位点的髓系特异性吸烟相关高甲基化特征。