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

: Carmeli Cristian, Kutalik Zoltán, Mishra Pashupati P., Porcu Eleonora, Delpierre Cyrille, Delaneau Olivier, Kelly-Irving Michelle, Bochud Murielle, Dhayat Nasser A., Ponte Belen, Pruijm Menno, Ehret Georg, Kähönen Mika, Lehtimäki Terho, Raitakari Olli T., Vineis Paolo, Kivimäki Mika, Chadeau-Hyam Marc, Dermitzakis Emmanouil, Vuilleumier Nicolas, Stringhini Silvia

Publisher: NATURE RESEARCH

: 2021

: Scientific Reports

: SCIENTIFIC REPORTS

: SCI REP-UK

: ARTN 3100

: 11

: 1

: 11

: 2045-2322

DOI: https://doi.org/10.1038/s41598-021-82714-2

: https://www.nature.com/articles/s41598-021-82714-2

: https://research.utu.fi/converis/portal/detail/Publication/53350803

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.

s41598-021-82714-2.pdf