Untargeted metabolomics reveals multiple metabolites influencing smoking-related DNA methylation

Epigenomics. 2018 Apr 1;10(4):379-393. doi: 10.2217/epi-2017-0101. Epub 2018 Mar 12.

Abstract

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.

Keywords: EWAS; epigenetic epidemiology; epigenetics; epigenome; exposome; metabolome; metabolome-wide association study; methylome; twin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Twin Study

MeSH terms

  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Genetic Association Studies
  • Humans
  • Male
  • Metabolomics
  • Middle Aged
  • Smoking / genetics*