Persistent epigenetic differences associated with prenatal exposure to famine in humans

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.

Fig. 1.

Difference in IGF2 DMR methylation between individuals prenatally exposed to famine and their same-sex sibling. (A) Periconceptional exposure: Difference in methylation according to the mother's last menstrual period (a common estimate of conception) before conception of the famine-exposed individual. (B) Exposure late in gestation: Difference in methylation according to the date of birth of the famine-exposed individual. To describe the difference in methylation according to estimated conception and birth dates, a lowess curve (red or blue) is drawn. The average distributed rations (in kcal/day) between December 1944 and June 1945 are depicted in green.