Epigenetic Biomarkers of Socioeconomic Status are Associated with Age-Related Chronic Diseases and Mortality in Older Adults

Abstract

AbstractLater-life health is patterned by socioeconomic influences across the lifecourse. However, the pathways underlying the biological embedding of socioeconomic status (SES) and its consequences on downstream morbidity and mortality are not fully understood. Epigenetic markers like DNA methylation (DNAm) may be promising surrogates of underlying biological processes that can enhance our understanding of how SES shapes population health. Studies have shown that SES is associated with epigenetic aging measures, but few have examined relationships between early and later-life SES and DNAm sites across the epigenome. In this study, we trained and tested DNAm-based surrogates, or “biomarkers,” of childhood and adult SES in two large, multi-racial/ethnic samples of older adults—the Health and Retirement Study (HRS) (N=3,527) and the Multi-Ethnic Study of Atherosclerosis (MESA) (N=1,182). Both biomarkers were associated with downstream morbidity and mortality, and these associations persisted after controlling for measured SES, and in some cases, epigenetic aging clocks. Both childhood and adult SES biomarker CpG sites were enriched for genomic features that regulate gene expression (e.g., DNAse hypersensitivity sites and enhancers) and were implicated in prior epigenome-wide studies of inflammation, aging, and chronic disease. Distinct patterns also emerged between childhood CpGs and immune system dysregulation and adult CpGs and metabolic functioning, health behaviors, and cancer. Results suggest DNAm-based surrogate biomarkers of SES may be useful proxies for unmeasured social exposures that can augment our understanding of the biological mechanisms between social disadvantage and downstream health.Significance StatementInformation on DNA methylation (DNAm)—an epigenetic modification that plays a central role in regulating gene expression—is increasingly available in large epidemiological studies. Since DNAm is relatively stable but responsive to environmental influences, genome-wide signatures are promising surrogates or biomarkers of exposure that may both shed light on biological mechanisms between adverse environments and downstream health and/or act as proxies for unmeasured exposures. To better understand the biological embedding of social disadvantage, this study trained and tested DNAm-based surrogates of childhood and adult socioeconomic status (SES) in two US-based cohorts of older adults. Findings reveal distinct DNAm signatures of SES that connect social adversity across the lifecourse with dysregulated immune system responses, inflammatory pathways, poorer metabolic functioning, chronic diseases, and cancer.