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

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

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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.

Original languageEnglish
Article number3100
JournalScientific Reports
Volume11
Issue number1
DOIs
Publication statusPublished - Feb 2021
Publication typeA1 Journal article-refereed

Publication forum classification

  • Publication forum level 1

ASJC Scopus subject areas

  • General

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