Smoking-related differenzial CpG methylation: a 27k discovery and replication study

Background: Tobacco smoking-associated diseases are a health problem of global scale. Epigenetic patterns including CpG methylation have been implicated in smoking-related pathology. Here, we present a genome-wide methylation study of smoking behaviour. Methods: The discovery round was conducted in 177 participants (current, former, and never smokers) of the epidemiological ESTHER study. Another 316 subjects served as an independent replication sample. Methylation patterns were analysed in peripheral blood DNA using the Infinium HumanMethylation27 BeadChip microarray. Validation and replication were done by Sequenom MassArray. Results: A single locus showed genome-wide significance for differenzial methylation by smoking behaviour in the discovery round, when using either parametric or non-parametric statistical methods. This finding was validated using the Sequenom assay and successfully replicated in the independent sample set. Conclusions: This genome-wide screen for differences in CpG methylation by smoking status identified a gene which might plausibly be involved in tobacco-related pathophysiology. Additional studies will have to address the functional implications of this finding for gene expression and clinical endpoints.