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Updated: May 16, 2026

Large-Scale Multi-Omics Genome-Wide Association Studies (Mo-GWAS): Guidelines for Sample Preparation and Normalization
Published on: July 27, 2021
Gene × environment interaction by a longitudinal epigenome-wide association study (LEWAS) overcomes limitations of
Debomoy K Lahiri1, Bryan Maloney
1Department of Psychiatry, Laboratory of Molecular Neurogenetics, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. dlahiri@iupui.edu
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.
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