Gene × environment interaction by a longitudinal epigenome-wide association study (LEWAS) overcomes limitations of genome-wide association study (GWAS)

通过纵向表观基因组关联研究(LEWAS)研究基因与环境的相互作用,克服了全基因组关联研究(GWAS)的局限性。

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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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