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 Vuilleumier; Silvia Stringhini

doi:10.1038/s41598-021-82714-2

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 Vuilleumier

Silvia Stringhini

^*Corresponding author for this work

Department of Clinical Chemistry

Research output: Contribution to journal › Article › Scientific › peer-review

12 Citations (Scopus)

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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 language	English
Article number	3100
Journal	Scientific Reports
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41598-021-82714-2
Publication status	Published - Feb 2021
Publication type	A1 Journal article-refereed

Funding

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.

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Carmeli, C., Kutalik, Z., Mishra, P. P., Porcu, E., Delpierre, C., Delaneau, O., Kelly-Irving, M., Bochud, M., Dhayat, N. A., Ponte, B., Pruijm, M., Ehret, G., Kähönen, M., Lehtimäki, T., Raitakari, O. T., Vineis, P., Kivimäki, M., Chadeau-Hyam, M., Dermitzakis, E., ... Stringhini, S. (2021). Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies. Scientific Reports, 11(1), Article 3100. https://doi.org/10.1038/s41598-021-82714-2

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

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.",

author = "Cristian Carmeli and Zolt{\'a}n Kutalik and Mishra, \{Pashupati P.\} and Eleonora Porcu and Cyrille Delpierre and Olivier Delaneau and Michelle Kelly-Irving and Murielle Bochud and Dhayat, \{Nasser A.\} and Belen Ponte and Menno Pruijm and Georg Ehret and Mika K{\"a}h{\"o}nen and Terho Lehtim{\"a}ki and Raitakari, \{Olli T.\} and Paolo Vineis and Mika Kivim{\"a}ki and Marc Chadeau-Hyam and Emmanouil Dermitzakis and Nicolas Vuilleumier and Silvia Stringhini",

note = "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; Yrj{\"o} 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 Kivim{\"a}ki 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: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = feb,

doi = "10.1038/s41598-021-82714-2",

language = "English",

volume = "11",

journal = "Scientific Reports",

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number = "1",

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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 & Stringhini, S 2021, 'Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies', Scientific Reports, vol. 11, no. 1, 3100. https://doi.org/10.1038/s41598-021-82714-2

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

SN - 2045-2322

VL - 11

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 3100

ER -

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

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