Implications of Genotype and Environment on Variation in DNA Methylation

Handbook of Nutrition, Diet, and Epigenetics pp 105-124| Cite as

• Authors
• Authors and affiliations

• Ives Y. Lim
• Xinyi Lin
• Neerja Karnani

1. 1.

Reference work entry

First Online: 05 January 2019

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Abstract

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.

Keywords

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

AHRR

Aryl-hydrocarbon receptor repressor

ASM

Allele-specific methylation

CGI

CpG islands

CNV

Copy number variation

CYP1A1

Cytochrome P450 family 1 subfamily A member 1

DNMT1

DNA methyltransferase 1

eQTL

Expression quantitative trait locus

EWAS

Epigenome-wide association study

FKBP5

FK506 binding protein 5

GNAS

Guanine nucleotide binding protein, Alpha stimulating

GRB10

Growth factor receptor bound protein 10

HIF1A

Hypoxia-inducible factor 1-alpha

LD

Linkage disequilibrium

MAT

Methionine adenosyltransferase

meQTL

Methylation quantitative trait locus

P-ASM

Parent-of-origin allele-specific methylation

PCR

Polymerase chain reaction

POP

Persistent organic pollutant

PTSD

Post-traumatic stress disorder

SAM

S-adenosylmethionine

S-ASM

Sequence-dependent allele-specific methylation

SNP

Single nucleotide polymorphism

TET

Ten-eleven translocation

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