Implications of Genotype and Environment on Variation in DNA Methylation

  • Ives Y. Lim
  • Xinyi Lin
  • Neerja KarnaniEmail author
Reference work entry


The epigenome is highly plastic and reacts to the changing external conditions such as diet, lifestyle, and toxins throughout the lifespan. Epigenome-wide association studies (EWAS) provide an opportunity to identify epigenetic variants associated with such exposures and the associated suboptimal health outcomes. DNA methylation at 5-methylcytosine is a routinely interrogated epigenetic mark in such EWAS studies. However, depending upon the choice of biological sample, a reliable quantification of the change in methylome at a genomic locus is often confounded by cellular heterogeneity. In addition, the interpretation of cause and effect of this methylation diversity in epigenomes is further complicated by the contributions from genotype and its interaction with the environment, thereby warranting a more sophisticated approach to reliably measure and interpret EWAS findings. This chapter discusses the factors influencing the variability in DNA methylome and its implications on biological interpretations.


DNA methylation Epigenome-wide association studies Cell heterogeneity meQTL Allele-specific methylation Epistasis Genotype Environment Metastable epialleles Gene-environment interactions Causality Nutrition 

List of Abbreviations


Aryl-hydrocarbon receptor repressor


Allele-specific methylation


CpG islands


Copy number variation


Cytochrome P450 family 1 subfamily A member 1


DNA methyltransferase 1


Expression quantitative trait locus


Epigenome-wide association study


FK506 binding protein 5


Guanine nucleotide binding protein, Alpha stimulating


Growth factor receptor bound protein 10


Hypoxia-inducible factor 1-alpha


Linkage disequilibrium


Methionine adenosyltransferase


Methylation quantitative trait locus


Parent-of-origin allele-specific methylation


Polymerase chain reaction


Persistent organic pollutant


Post-traumatic stress disorder




Sequence-dependent allele-specific methylation


Single nucleotide polymorphism


Ten-eleven translocation


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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Singapore Institute for Clinical Sciences (SICS)A*STAR, Brenner Centre for Molecular MedicineSingaporeSingapore

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