Journal Article

DKFZ-2022-02135

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.

Fiorito, G. ; Pedron, S. ; Ochoa-Rosales, C. ; McCrory, C. ; Polidoro, S. ; Zhang, Y.DKFZ* ; Dugué, P.-A. ; Ratliff, S. ; Zhao, W. N. ; McKay, G. J. ; Costa, G. ; Solinas, M. G. ; Harris, K. M. ; Tumino, R. ; Grioni, S. ; Ricceri, F. ; Panico, S. ; Brenner, H.DKFZ* ; Schwettmann, L. ; Waldenberger, M. ; Matias-Garcia, P. R. ; Peters, A. ; Hodge, A. ; Giles, G. G. ; Schmitz, L. L. ; Levine, M. ; Smith, J. A. ; Liu, Y. ; Kee, F. ; Young, I. S. ; McGuinness, B. ; McKnight, A. J. ; van Meurs, J. ; Voortman, T. ; Kenny, R. A. ; consortium, L. (Collaboration Author) ; Vineis, P. ; Carmeli, C.

2022
Oxford Univ. Pr. Oxford [u.a.]

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Please use a persistent id in citations: doi:10.1093/gerona/glac041

Abstract: Educational inequalities in all-cause mortality have been observed for decades. However, the underlying biological mechanisms are not well known. We aimed to assess the role of DNA methylation changes in blood captured by epigenetic clocks in explaining these inequalities. Data were from 8 prospective population-based cohort studies, representing 13 021 participants. First, educational inequalities and their portion explained by Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, and DNAmGrimAge epigenetic clocks were assessed in each cohort via counterfactual-based mediation models, on both absolute (hazard difference) and relative (hazard ratio) scales, and by sex. Second, estimates from each cohort were pooled through a random effect meta-analysis model. Men with low education had excess mortality from all causes of 57 deaths per 10 000 person-years (95% confidence interval [CI]: 38, 76) compared with their more advantaged counterparts. For women, the excess mortality was 4 deaths per 10 000 person-years (95% CI: -11, 19). On the relative scale, educational inequalities corresponded to hazard ratios of 1.33 (95% CI: 1.12, 1.57) for men and 1.15 (95% CI: 0.96, 1.37) for women. DNAmGrimAge accounted for the largest proportion, approximately 50%, of the educational inequalities for men, while the proportion was negligible for women. Most of this mediation was explained by differential effects of unhealthy lifestyles and morbidities of the World Health Organization (WHO) risk factors for premature mortality. These results support DNA methylation-based epigenetic aging as a signature of educational inequalities in life expectancy emphasizing the need for policies to address the unequal social distribution of these WHO risk factors.

Keyword(s): Educational Status (MeSH) ; Epigenesis, Genetic (MeSH) ; Epigenomics (MeSH) ; Female (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Mortality (MeSH) ; Prospective Studies (MeSH) ; Risk Factors (MeSH) ; Socioeconomic Factors (MeSH) ; Biomarkers ; DNA methylation ; Longevity ; Social inequalities

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Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2022

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Current Contents - Social and Behavioral Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Social Sciences Citation Index ; Web of Science Core Collection

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