Skip to main content

Advertisement

Log in

DNA Methylation–Based Biomarkers of Environmental Exposures for Human Population Studies

  • Topical Collection on Environmental Epigenetics (A Cardenas and A Kupsco, Section Editors)
  • Published:
Current Environmental Health Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This manuscript orients the reader to the underlying motivations of environmental biomarker development for human population studies and provides the foundation for applying these novel biomarkers in future research. In this review, we focus our attention on the DNA methylation–based biomarkers of (i) smoking, among adults and pregnant women, (ii) lifetime cannabis use, (iii) alcohol consumption, and (iv) cumulative exposure to lead.

Recent Findings

Prior environmental exposures and lifestyle modulate DNA methylation levels. Exposure-related DNA methylation changes can either be persistent or reversible once the exposure is no longer present, and this combination of both persistent and reversible changes has essential value for biomarker development. Here, we present available biomarkers representing past and cumulative exposures using individual DNA methylation profiles.

Summary

In the present work, we describe how the field of environmental epigenetics can leverage machine learning algorithms to develop exposure biomarkers and reduce problems of misreporting exposures or limited access technology. We emphasize the crucial role of the individual DNA methylation profiles in those predictions, providing a summary of each biomarker, and highlighting their advantages, and limitations. Future research can cautiously leverage these DNA methylation–based biomarkers to understand the onset and progression of diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Barros SP, Offenbacher S. Epigenetics: connecting environment and genotype to phenotype and disease. J Dent Res. 2009;88(5):400–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Leenen FA, Muller CP, Turner JD. DNA methylation: conducting the orchestra from exposure to phenotype? Clin Epigenetics. 2016;8:92.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Marioni RE, Shah S, McRae AF, et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol. 2015;16(1):25.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Byun HM, Colicino E, Trevisi L, et al. Effects of air pollution and blood mitochondrial DNA methylation on markers of heart rate variability. J Am Heart Assoc Cardiovas Cerebrovas Dis. 2016;5(4):e003218.

    Google Scholar 

  5. Agha G, Mendelson MM, Ward-Caviness CK, Joehanes R, Huan T, Gondalia R, et al. Blood leukocyte DNA methylation predicts risk of future myocardial infarction and coronary heart disease. Circulation. 2019;140(8):645–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Wu S, Hivert MF, Cardenas A, Zhong J, Rifas-Shiman SL, Agha G, et al. Exposure to low levels of lead in utero and umbilical cord blood DNA methylation in project viva: an epigenome-wide association study. Environ Health Perspect. 2017;125(8):087019.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Wright RO, Schwartz J, Wright RJ, Bollati V, Tarantini L, Park SK, et al. Biomarkers of lead exposure and DNA methylation within retrotransposons. Environ Health Perspect. 2010;118(6):790–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bitto A, Pizzino G, Irrera N, Galfo F, Squadrito F. Epigenetic modifications due to heavy metals exposure in children living in polluted areas. Curr Genomics. 2014;15(6):464–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. •• Reese SE, Zhao S, Wu MC, Joubert BR, Parr CL, Håberg SE, et al. DNA methylation score as a biomarker in newborns for sustained maternal smoking during pregnancy. Environ Health Perspect. 2017;125(4):760–6. This manuscript describes of the smoking biomarker during pregnancy.

    Article  CAS  PubMed  Google Scholar 

  10. Joubert BR, Haberg SE, Nilsen RM, et al. 450K epigenome-wide scan identifies differential DNA methylation in newborns related to maternal smoking during pregnancy. Environ Health Perspect. 2012;120(10):1425–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, et al. Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med. 2009;179(7):572–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ladd-Acosta C. Epigenetic signatures as biomarkers of exposure. Cur Environ Health Rep. 2015;2(2):117–25.

    Article  CAS  Google Scholar 

  13. Ladd-Acosta C, Fallin MD. DNA methylation signatures as biomarkers of prior environmental exposures. Cur Epidemiol Rep. 2019;6(1):1–13.

    Article  Google Scholar 

  14. Richmond RC, Suderman M, Langdon R, et al. DNA methylation as a marker for prenatal smoke exposure in adults. Int J Epidemiol. 2018;47(4):1120–30.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Cardenas A, Rifas-Shiman SL, Agha G, Hivert MF, Litonjua AA, DeMeo D, et al. Persistent DNA methylation changes associated with prenatal mercury exposure and cognitive performance during childhood. Sci Rep. 2017;7(1):288.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. •• Bollepalli S, Korhonen T, Kaprio J, Anders S, Ollikainen M. EpiSmokEr: a robust classifier to determine smoking status from DNA methylation data. Epigenomics. 2019;11(13):1469–86. This manuscript describes of the smoking biomarker.

    Article  CAS  PubMed  Google Scholar 

  17. Zeilinger S, Kuhnel B, Klopp N, et al. Tobacco smoking leads to extensive genome-wide changes in DNA methylation. PLoS One. 2013;8(5):e63812.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. McCartney DL, Stevenson AJ, Hillary RF, Walker RM, Bermingham ML, Morris SW, et al. Epigenetic signatures of starting and stopping smoking. EBioMedicine. 2018;37:214–20.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Joehanes R, Just AC, Marioni RE, Pilling LC, Reynolds LM, Mandaviya PR, et al. Epigenetic signatures of cigarette smoking. Circ Cardiovasc Genet. 2016;9(5):436–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Rakyan VK, Down TA, Balding DJ, Beck S. Epigenome-wide association studies for common human diseases. Nat Rev Genet. 2011;12(8):529–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Feinberg AP. Epigenomics reveals a functional genome anatomy and a new approach to common disease. Nat Biotechnol. 2010;28(10):1049–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Portela A, Esteller M. Epigenetic modifications and human disease. Nat Biotechnol. 2010;28(10):1057–68.

    Article  CAS  PubMed  Google Scholar 

  23. Zou H, Hastie T. Regularization and variable selection via the elastic net. J Royal Statis Soc Ser B. 2005;67(2):301–20.

    Article  Google Scholar 

  24. Tibshirani R. Regression shrinkage and selection via the Lasso. J R Stat Soc Ser B Methodol. 1996;58(1):267–88.

    Google Scholar 

  25. •• Colicino E, Just A, Kioumourtzoglou MA, et al. Blood DNA methylation biomarkers of cumulative lead exposure in adults. J Exposure Sci Environ Epidemiol. 2019. This manuscript describes of the lead exposure biomarkers.

  26. •• Markunas CA, Hancock DB, Xu Z, et al. Epigenome-wide analysis uncovers a blood-based DNA methylation biomarker of lifetime cannabis use. bioRxiv. 2019:620641. This manuscript describes of the cannabis biomarker.

  27. Gao X, Zhang Y, Breitling LP, Brenner H. Relationship of tobacco smoking and smoking-related DNA methylation with epigenetic age acceleration. Oncotarget. 2016;7(30):46878–89.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Nwanaji-Enwerem JC, Cardenas A, Chai PR, et al. Relationships of long-term smoking and moist snuff consumption with a DNA methylation age relevant smoking index: an analysis in buccal cells. Nicotine Tob Res. 2018;21(9):1267–73.

    Article  PubMed Central  Google Scholar 

  29. • Philibert R, Dogan M, Beach SRH, et al. AHRR methylation predicts smoking status and smoking intensity in both saliva and blood DNA. Am J Med Genetic B Neuropsychiatr Genet. 2020;183(1):51–60. This manuscript describes the role of a few CpGs in the prediction of smoking status.

    Article  CAS  Google Scholar 

  30. Gao X, Jia M, Zhang Y, et al. DNA methylation changes of whole blood cells in response to active smoking exposure in adults: a systematic review of DNA methylation studies. Clin Epigenetics. 2015;7:113.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Volkow ND, Baler RD, Compton WM, Weiss SR. Adverse health effects of marijuana use. N Engl J Med. 2014;370(23):2219–27.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Lafaye G, Karila L, Blecha L, Benyamina A. Cannabis, cannabinoids, and health. Dialogues Clin Neurosci. 2017;19(3):309–16.

    PubMed  PubMed Central  Google Scholar 

  33. Andersen AM, Dogan MV, Beach SRH, Philibert RA. Current and future prospects for epigenetic biomarkers of substance use disorders. Genes (Basel). 2015;6(4):991–1022.

    Article  CAS  Google Scholar 

  34. Huestis MA. Human cannabinoid pharmacokinetics. Chem Biodivers. 2007;4(8):1770–804.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Steyerberg EW, Harrell FE Jr. Prediction models need appropriate internal, internal-external, and external validation. J Clin Epidemiol. 2016;69:245–7.

    Article  PubMed  Google Scholar 

  36. Limosin F. Epidemiologic warnings from studies on alcohol use disorders. L'Encephale. 2014;40(2):129–35.

    Article  CAS  PubMed  Google Scholar 

  37. Allen JP. Use of biomarkers of heavy drinking in health care practice. Mil Med. 2003;168(5):364–7.

    Article  PubMed  Google Scholar 

  38. •• Liu C, Marioni RE, Hedman AK, Pfeiffer L, Tsai PC, Reynolds LM, et al. A DNA methylation biomarker of alcohol consumption. Mol Psychiatry. 2018;23(2):422–33. This manuscript describes of the alcohol consumption biomarkers.

    Article  CAS  PubMed  Google Scholar 

  39. Jin Z, Mendu SK, Birnir B. GABA is an effective immunomodulatory molecule. Amino Acids. 2013;45(1):87–94.

    Article  CAS  PubMed  Google Scholar 

  40. Bakulski KM, Rozek LS, Dolinoy DC, Paulson HL, Hu H. Alzheimer’s disease and environmental exposure to lead: the epidemiologic evidence and potential role of epigenetics. Curr Alzheimer Res. 2012;9(5):563–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Holland MG, Cawthon D. Levels ATFoBL. workplace lead exposure. J Occup Environ Med. 2016;58(12):e371–e4.

    Article  CAS  PubMed  Google Scholar 

  42. Weisskopf MG, Proctor SP, Wright RO, et al. Cumulative lead exposure and cognitive performance among elderly men. Epidemiol. 2007;18(1):59–66.

    Article  Google Scholar 

  43. Hu H, Shih R, Rothenberg S, Schwartz BS. The epidemiology of lead toxicity in adults: measuring dose and consideration of other methodologic issues. Environ Health Perspect. 2007;115(3):455–62.

    Article  CAS  PubMed  Google Scholar 

  44. Navas-Acien A, Schwartz BS, Rothenberg SJ, et al. Bone lead levels and blood pressure endpoints: a meta-analysis. Epidemiol. 2008;19(3):496–504.

    Article  Google Scholar 

  45. Hu H, Rabinowitz M, Smith D. Bone lead as a biological marker in epidemiologic studies of chronic toxicity: conceptual paradigms. Environ Health Perspect. 1998;106(1):1–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Wilker E, Korrick S, Nie LH, Sparrow D, Vokonas P, Coull B, et al. Longitudinal changes in bone lead levels: the VA normative aging study. J Occup Environ Med. 2011;53(8):850–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Handy DE, Castro R, Loscalzo J. Epigenetic modifications: basic mechanisms and role in cardiovascular disease. Circulation. 2011;123(19):2145–56.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Chen BH, Marioni RE, Colicino E, Peters MJ, Ward-Caviness CK, Tsai PC, et al. DNA methylation-based measures of biological age: meta-analysis predicting time to death. Aging. 2016;8(9):1844–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. • Valeri L, Reese SL, Zhao S, Page CM, Nystad W, Coull BA, et al. Misclassified exposure in epigenetic mediation analyses. Does DNA methylation mediate effects of smoking on birthweight? Epigenomics. 2017;9(3):253–65. This manuscript identifies the critical role of misclassified exposure in epidemiology.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

EC was supported by the National Institute on Minority Health and Health Disparities (NIMHD) (R01MD013310) and by the National Institute of Environmental Health Sciences (NIEHS) (P30ES023515, U2CES026444, and UH3OD023337). JCN was supported by a NIH/NIA Ruth L. Kirschstein National Research Service Award (1 F31AG056124-01A1).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elena Colicino.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Environmental Epigenetics

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nwanaji-Enwerem, J.C., Colicino, E. DNA Methylation–Based Biomarkers of Environmental Exposures for Human Population Studies. Curr Envir Health Rpt 7, 121–128 (2020). https://doi.org/10.1007/s40572-020-00269-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40572-020-00269-2

Keywords

Navigation