Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two European cohort studies

Abstract

Individuals growing up during childhood in a socioeconomically disadvantaged family experience a higher rate of inflammation-related diseases later in life. Little is known about the mechanisms linking early life experiences to the functioning of the immune system decades later. Here we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation (C-reactive protein) and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (up to 78%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than DNA methylation potentially regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of pro-inflammatory genes regulation that cannot fully be explained by differential DNA methylation.