Untargeted metabolomics reveals multiple metabolites influencing smoking-related DNA methylation

  • Epigenomics. 2018 Apr 1;10(4):379-393. doi: 10.2217/epi-2017-0101.
Yunfeng Huang  1 ,  Qin Hui  1 ,  Douglas I Walker  2 ,  Karan Uppal  2 ,  Jack Goldberg  3 ,  Dean P Jones  2 ,  Viola Vaccarino  1 ,  Yan V Sun  1  4
Affiliations
  • 1. Department of Epidemiology, Emory University Rollins School of Public Health, Atlanta, GA 30322, USA.
  • 2. Department of Medicine, Division of Pulmonary, Allergy & Critical Care Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
  • 3. Vietnam Era Twin Registry, VA Epidemiologic Research & Information Center & Department of Epidemiology, University of Washington School of Public Health, Seattle, WA 98195, USA.
  • 4. Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA 30322, USA.
PMID: 29528243 DOI: 10.2217/epi-2017-0101
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.
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