Untargeted metabolomics reveals multiple metabolites influencing smoking-related DNA methylation.

AIM: We conducted a joint metabolomic-epigenomic study to identify patterns of epigenetic associations with smoking-related metabolites.

PATIENTS & METHODS: We performed an untargeted metabolome-wide association study of smoking and epigenome-wide association studies of smoking-related metabolites among 180 male twins. We examined the patterns of epigenetic association linked to smoking-related metabolites using hierarchical clustering.

RESULTS: Among 12 annotated smoking-related metabolites identified from a metabolome-wide association study, we observed significant hypomethylation associated with increased level of N-acetylpyrrolidine, cotinine, 5-hydroxycotinine and nicotine and hypermethylation associated with increased level of 8-oxoguanine. Hierarchical clustering revealed common and unique epigenetic-metabolic associations related to smoking.

CONCLUSION: Our study suggested that a joint metabolome-epigenome approach can reveal additional details in molecular responses to the environmental exposure to understand disease risk.