The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis
Year: 2022
Type: review
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.
Authors: Giovanni Fiorito, Sara Pedron, Carolina Ochoa-Rosales, Cathal McCrory, Silvia Polidoro, Yan Zhang, Pierre-Antoine Dugué, Scott Ratliff, Wei N Zhao, Gareth J McKay, Giuseppe Costa, Maria Giuliana Solinas, Kathleen Mullan Harris, Rosario Tumino, Sara Grioni, Fulvio Ricceri, Salvatore Panico, Hermann Brenner, Lars Schwettmann, Melanie Waldenberger, Pamela R Matias-Garcia, Annette Peters, Allison Hodge, Graham G Giles, Lauren L Schmitz, Morgan Levine, Jennifer A Smith, Yongmei Liu, Frank Kee, Ian S Young, Bernadette McGuinness, Amy Jayne McKnight, Joyce van Meurs, Trudy Voortman, Rose A Kenny, Paolo Vineis, Cristian Carmeli
Institutions: University of Sassari, MRC Centre for Environment and Health, Imperial College London, Helmholtz Munich, Technical University of Munich, University of Concepción, Erasmus MC, Trinity College Dublin, Italian institute for Genomic Medicine, German Cancer Research Center, The University of Melbourne, Cancer Council Victoria, University of Michigan, Queen's University Belfast, University of Turin, University of North Carolina at Chapel Hill, Fondazione IRCCS Istituto Nazionale dei Tumori, Federico II University Hospital, University of Naples Federico II, Heidelberg University, Martin Luther University Halle-Wittenberg, German Centre for Cardiovascular Research, University of Wisconsin–Madison, Yale University, Institute for Social Research, Duke University, University of Fribourg
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: G1301969567, G1502031688, G1953887145, G3344327863, G434337789, A Social Epigenomic Approach to Health Disparities in Cardiovascular Risk Factors, G7387336387, G7660514405, G8564457728, The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) - CAPI, Lifecourse biological pathways underlying social differences in healthy ageing, Life Course Determinants of Epigenetic Age Acceleration and Subsequent Dementia
OpenAlex ID: W4213063573