In a study published in Nature Communications, a team led by Profs Andrew TESCHENDORFF and WANG Sijia, both from the CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences, addressed this problem by performing the first ever meta-analysis of whole blood EWAS in a cell-lineage specific manner.  

The researchers focused on smoking and assembled DNAm data from seven independent EWAS, including the first Chinese cohort where smoking associated DNAm changes have been comprehensively mapped.  

The analysis of the data revealed that smoking-associated DNAm changes are largely independent of ethnicity, justifying the merging of Chinese and white Caucasian cohorts for a meta-analysis.  

The meta-analysis further revealed how most of the DNAm changes in blood occur within the myeloid lineage, mapping preferentially to DNase hypersensitive sites (DHS) characteristic of inflammatory monocytes and macrophages.  

Importantly, the analysis revealed a novel myeloid-specific DNAm signature associated with acute myeloid leukemia, a hematological cancer for which smoking is a moderate risk factor. In contrast, the study did not find many DNAm alterations within the lymphoid lineage. 

“This study demonstrates that it is possible to use a computational approach to infer cell-type specific DNAm changes, thus avoiding the need for extremely laborious and expensive cell-sorting. We hope that it may serve as a paradigm for performing similar meta-analysis of EWAS in a cell-type specific manner,” said Prof. Andrew TESCHENDORFF.