Gene × Environment Interaction by a Longitudinal Epigenome-Wide Association Study (LEWAS) Overcomes Limitations of Genome-Wide Association Study (GWAS)

Abstract

The goal of genome-wide association studies is to identify SNPs unique to disease. It usually involves a single sampling from subjects‘ lifetimes. While primary DNA sequence variation influences gene-expression levels, expression is also influenced by epigenetics, including the ‘somatic epitype‘ (G_SE), an epigenotype acquired postnatally. While genes are inherited, and novel polymorphisms do not routinely appear, G_SE is fluid. Furthermore, G_SE could respond to environmental factors (such as heavy metals) and to differences in exercise, maternal care and dietary supplements – all of which postnatally modify oxidation or methylation of DNA, leading to altered gene expression. Change in epigenetic status may be critical for the development of many diseases. We propose a ‘longitudinal epigenome-wide association study‘, wherein G_SE are measured at multiple time points along with subjects‘ histories. This Longitudinal epigenome-wide association study, based on the ‘dynamic‘ somatic epitype over the ‘static‘ genotype, merits further investigation.

KEYWORDS::

• association study
• environment
• epigenetics
• epigenomics
• genomics
• GWAS
• LEWAS

Financial & competing interests disclosure

The authors sincerely appreciate the grant support from the Alzheimer‘s Association (Zenith award and IIRG) and the National Institute on Aging/NIH (AG18379 and AG18884) to DK Lahiri. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors sincerely appreciate the grant support from the Alzheimer‘s Association (Zenith award and IIRG) and the National Institute on Aging/NIH (AG18379 and AG18884) to DK Lahiri. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.