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The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.

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.

SUBMITTER: Fiorito G

PROVIDER: S-EPMC10310990 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.

Fiorito Giovanni G Pedron Sara S Ochoa-Rosales Carolina C McCrory Cathal C Polidoro Silvia S Zhang Yan Y Dugué Pierre-Antoine PA Ratliff Scott S Zhao Wei N WN McKay Gareth J GJ Costa Giuseppe G Solinas Maria Giuliana MG Harris Kathleen Mullan KM Tumino Rosario R Grioni Sara S Ricceri Fulvio F Panico Salvatore S Brenner Hermann H Schwettmann Lars L Waldenberger Melanie M Matias-Garcia Pamela R PR Peters Annette A Hodge Allison A Giles Graham G GG Schmitz Lauren L LL Levine Morgan M Smith Jennifer A JA Liu Yongmei Y Kee Frank F Young Ian S IS McGuinness Bernadette B McKnight Amy Jayne AJ van Meurs Joyce J Voortman Trudy T Kenny Rose A RA Vineis Paolo P Carmeli Cristian C

The journals of gerontology. Series A, Biological sciences and medical sciences 20220901 9

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 epig ...[more]

PMID: 35172329

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Project description:To evaluate trends in premature cancer mortality in Colombia by educational level in three periods: 1998-2002 with low healthcare insurance coverage, 2003-2007 with rapidly increasing coverage and finally 2008-2012 with almost universal coverage (2008-2012).Colombian population-based, national secondary mortality data.We included all (n=188,091) cancer deaths occurring in the age group 20-64 years between 1998 and 2012, excluding only cases with low levels of quality of registration (n=2902, 1.5%).In this descriptive study, we linked mortality data of ages 20-64 years to census data to obtain age-standardised cancer mortality rates by educational level. Using Poisson regression, we modelled premature mortality by educational level estimating rate ratios (RR), relative index of inequality (RII) and the Slope Index of Inequality (SII).Relative measures showed increased risks of dying among the lower educated compared to the highest educated; this tendency was stronger in women (RRprimary 1.49; RRsecondary 1.22, both p<0.0001) than in men (RRprimary 1.35; RRsecondary 1.11, both p<0.0001). In absolute terms (SII), cancer caused a difference per 100 000 deaths between the highest and lowest educated of 20.5 in males and 28.5 in females. RII was significantly higher among women and the younger age categories. RII decreased between the first and second periods; afterwards (2008-2012), it increased significantly back to their previous levels. Among women, no significant increases or declines in cancer mortality over time were observed in recent periods in the lowest educated group, whereas strong recent declines were observed in those with secondary education or higher.Educational inequalities in cancer mortality in Colombia are increasing in absolute and relative terms, and are concentrated in young age categories. This trend was not curbed by increases in healthcare insurance coverage. Policymakers should focus on improving equal access to prevention, early detection, diagnostic and treatment facilities.

Project description:BackgroundEducational inequalities in health and mortality in European countries have often been studied in the context of welfare regimes or political systems. We argue that the healthcare system is the national level feature most directly linkable to mortality amenable to healthcare. In this article, we ask to what extent the strength of educational differences in mortality amenable to healthcare vary among European countries and between European healthcare system types.MethodsThis study uses data on mortality amenable to healthcare for 21 European populations, covering ages 35-79 and spanning from 1998 to 2006. ISCED education categories are used to calculate relative (RII) and absolute inequalities (SII) between the highest and lowest educated. The healthcare system typology is based on the latest available classification. Meta-analysis and ANOVA tests are used to see if and how they can explain between-country differences in inequalities and whether any healthcare system types have higher inequalities.ResultsAll countries and healthcare system types exhibited relative and absolute educational inequalities in mortality amenable to healthcare. The low-supply and low performance mixed healthcare system type had the highest inequality point estimate for the male (RII = 3.57; SII = 414) and female (RII = 3.18; SII = 209) population, while the regulation-oriented public healthcare systems had the overall lowest (male RII = 1.78; male SII = 123; female RII = 1.86; female SII = 78.5). Due to data limitations, results were not robust enough to make substantial claims about typology differences.ConclusionsThis article aims at discussing possible mechanisms connecting healthcare systems, social position, and health. Results indicate that factors located within the healthcare system are relevant for health inequalities, as inequalities in mortality amenable to medical care are present in all healthcare systems. Future research should aim at examining the role of specific characteristics of healthcare systems in more detail.

Dataset Information

The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.

Publications

The Role of Epigenetic Clocks in Explaining Educational Inequalities in Mortality: A Multicohort Study and Meta-analysis.

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