Persistent epigenetic differences associated with prenatal exposure to famine in humans

TLDR

Early adverse environmental conditions are linked to adult disease risk, and epigenetic dysregulation is a proposed mechanism. Individuals prenatally exposed to the Dutch Hunger Winter had lower IGF2 DNA methylation six decades later compared to unexposed siblings, an effect specific to periconceptional exposure that supports persistent epigenetic changes from early life.

Abstract

Extensive epidemiologic studies have suggested that adult disease risk is associated with adverse environmental conditions early in development. Although the mechanisms behind these relationships are unclear, an involvement of epigenetic dysregulation has been hypothesized. Here we show that individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944-45 had, 6 decades later, less DNA methylation of the imprinted IGF2 gene compared with their unexposed, same-sex siblings. The association was specific for periconceptional exposure, reinforcing that very early mammalian development is a crucial period for establishing and maintaining epigenetic marks. These data are the first to contribute empirical support for the hypothesis that early-life environmental conditions can cause epigenetic changes in humans that persist throughout life.