Gaps in Knowledge and Missing Evidence in the Role of DNA Methylation in Biological Embedding

  • Christiana A. DemetriouEmail author
  • Karin van Veldhoven
  • Caroline Relton
  • Silvia Stringhini
  • Kyriacos Kyriacou
  • Paolo Vineis
Reference work entry


The thrifty phenotype hypothesis – the theory that under- or malnutrition during gestation could permanently influence the body’s structure and function contributing to adult disease – has then been closely linked with biological embedding, the process through which external exposures “get under the skin” to influence human biological processes.

Biological embedding has been hypothesized to occur through three different processes which may often coexist: latent effects, cumulative effects, and pathway effects. Irrespective of the exact mechanism, in order for biological embedding to occur, responses to an environmental signal need to be stage dependent, heritable, and persistent. Such phenotypic effects can be explained by epigenetic modifications imposed by environmental signals, which are themselves heritable, time dependent, and tissue as well as sex specific. DNA methylation is the epigenetic mechanism that has been most extensively studied in this context.

The synthesis of current research relating to the biological embodiment of early-life exposures through DNA methylation provides some support to the involvement of DNA methylation in biological embedding and provides evidence for a mechanism through which early-life exposures can affect disease risk later in life.

However, there still remain several gaps in knowledge which are discussed in this chapter. In order to generate evidence that will strongly support and further elucidate the role of DNA methylation in biological embedding of early-life exposures, these gaps need to be addressed in more and better designed studies.


Biological embedding Thrifty phenotype hypothesis Developmental plasticity DNA methylation Epigenetics Exposome Early-life nutrition Early-life socioeconomic status Childhood obesity Childhood overweight Chronic disease 

List of Abbreviations




5′—C—phosphate—G—3′, cytosine and guanine separated by only one phosphate


Insulin-like growth factor-2


Socioeconomic status


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Christiana A. Demetriou
    • 1
    • 2
    Email author
  • Karin van Veldhoven
    • 3
  • Caroline Relton
    • 4
    • 5
  • Silvia Stringhini
    • 6
  • Kyriacos Kyriacou
    • 7
  • Paolo Vineis
    • 3
  1. 1.Neurology Clinic DThe Cyprus Institute of Neurology and GeneticsAyios DhometiosCyprus
  2. 2.The Cyprus School of Molecular MedicineThe Cyprus Institute of Neurology and GeneticsAyios DhometiosCyprus
  3. 3.Department of Epidemiology and BiostatisticsSchool of Public Health, Imperial College LondonLondonUK
  4. 4.MRC Integrative Epidemiology Unit, School of Social and Community MedicineUniversity of BristolBristolUK
  5. 5.Institute of Genetic MedicineNewcastle UniversityNewcastle upon TyneUK
  6. 6.Institute of Social and Preventive Medicine (IUMSP)Lausanne University HospitalLausanneSwitzerland
  7. 7.Department of Electron Microscopy/Molecular PathologyThe Cyprus Institute of Neurology and Genetics, The Cyprus School of Molecular MedicineThe Cyprus School of MolecularCyprus

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