1. Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies.
- Author
-
Carmeli C, Kutalik Z, Mishra PP, Porcu E, Delpierre C, Delaneau O, Kelly-Irving M, Bochud M, Dhayat NA, Ponte B, Pruijm M, Ehret G, Kähönen M, Lehtimäki T, Raitakari OT, Vineis P, Kivimäki M, Chadeau-Hyam M, Dermitzakis E, Vuilleumier N, and Stringhini S
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers blood, C-Reactive Protein immunology, Child, DNA Methylation, Female, Finland, Gene Expression Profiling, Humans, Inflammation immunology, Inflammation pathology, Life Change Events, Longitudinal Studies, Male, Middle Aged, Models, Statistical, Socioeconomic Factors, Switzerland, Vulnerable Populations psychology, C-Reactive Protein genetics, Epigenesis, Genetic, Immune System metabolism, Inflammation genetics, Transcriptome
- Abstract
Individuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation 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 (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation.
- Published
- 2021
- Full Text
- View/download PDF