TY - JOUR
T1 - Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies
AU - Carmeli, Cristian
AU - Kutalik, Zoltán
AU - Mishra, Pashupati P.
AU - Porcu, Eleonora
AU - Delpierre, Cyrille
AU - Delaneau, Olivier
AU - Kelly-Irving, Michelle
AU - Bochud, Murielle
AU - Dhayat, Nasser A.
AU - Ponte, Belen
AU - Pruijm, Menno
AU - Ehret, Georg
AU - Kähönen, Mika
AU - Lehtimäki, Terho
AU - Raitakari, Olli T.
AU - Vineis, Paolo
AU - Kivimäki, Mika
AU - Chadeau-Hyam, Marc
AU - Dermitzakis, Emmanouil
AU - Vuilleumier, Nicolas
AU - Stringhini, Silvia
N1 - Funding Information:
This work was supported by the European Commission [grant Horizon 2020 number 633666] and the Swiss State Secretariat for Education, Research and Innovation SERI, and by an Ambizione Grant from the Swiss National Science Foundation (PZ00P3_147998). The YFS study has been financially supported by the Academy of Finland: Grants 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (Grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research ; Finnish Cultural Foundation; The Sigrid Juselius Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; Diabetes Research Foundation of Finnish Diabetes Association; EU Horizon 2020 (Grant 755320 for TAXINOMISIS); European Research Council (Grant 742927 for MULTIEPIGEN project); and Tampere University Hospital Supporting Foundation. The SKIPOGH study was supported by a grant from the Swiss National Science Foundation [Grant Number 33CM30-124087]. M Kivimäki is supported by the UK Medical Research Council (R024227, S011676), US National Institute on Aging (NIH, R01AG056477), NordForsk and the Academy of Finland (311492). Z Kutalik was supported by the Swiss National Science Foundation (31003A_169929). We are grateful to the CHARGE consortium for sharing their association summary statistics.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/2
Y1 - 2021/2
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-021-82714-2
DO - 10.1038/s41598-021-82714-2
M3 - Article
C2 - 33542415
AN - SCOPUS:85100491749
VL - 11
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 3100
ER -