Smoking is a major risk factor for some complex diseases. Epigenetic changes, especially DNA methylation (DNAm) changes, are believed to play an important role in increasing the risk of disease. A large number of existing epigenome association studies (EWAS) have explored how smoking affects DNA methylation in normal cells by mapping DNAm changes in the blood. However, blood is made up of many different types of cells, so it is not clear which specific cell types are more likely to be affected by smoking.
The research team used a cell-specific method to perform Meta analysis of blood EWAS to solve this problem for the first time. The researchers collected and analyzed DNA methylation data from seven independent EWAS cohorts, including the first Chinese cohort to conduct a comprehensive analysis of smoking-related DNAm changes. The study found that the DNAm changes related to smoking are largely independent of race, supporting the rationality of combining multi-ethnic cohorts for meta-analysis. Meta analysis further reveals how most smoking-related DNAm changes in the blood occur in bone marrow cell lines, and mainly appear on DNase hypersensitivity sites of inflammatory monocytes and macrophages. The newly discovered myeloid-specific DNAm signal associated with smoking is associated with acute myeloid leukemia. Smoking is a moderate risk factor for acute myeloid leukemia. However, there are not too many DNAm changes associated with smoking in lymphocytes.