Abstract
This latest in our series of papers describes transgenerational methylation related to mid-childhood food availability in 19th century Överkalix, Sweden. Failed vs.bountiful crops differentially influenced methylation in grandchildren of exposed paternal grandparents. In this case study of 8 tracked cases with differential ancestral exposure, adult progeny differed in methylated CpGs in three Amigo site gene pathways: “insulin processing”, “adipose tissue growth” and “hypothalamic development”, reflecting famine, excess food and reaction to food-insecurity stress. This is the first demonstration of transgenerational epigenetic inheritance in humans following grandparental childhood exposure, an early developmental origin of adult disease.
Non-technical summary Paternal grandparent food supply preceding their prepubertal growth spurt induced epigenetic marks in three gene pathways reflecting famine, excess food and reaction to food-insecurity stress. Our epidemiological findings of adverse transgenerational effects of ancestral overnutrition and conversely, beneficial effects of famine during SGP1 prompted us to study individuals whose paternal grandparents were randomly exposed, during their Slow Growth Period (SGP) - a sensitive period preceding the pre-pubertal growth spurt - to failed or bumper crops potentially engendering epigenetic marks on mechanistic molecular gene pathways.