An integrative framework and recommendations for the study of DNA methylation in the context of race and ethnicity

Abstract

Human social epigenomics research is critical to elucidate the intersection of social and genetic influences underlying racial and ethnic differences in health and development. However, this field faces major challenges in both methodology and interpretation with regard to disentangling confounded social and biological aspects of race and ethnicity. To address these challenges, we discuss how these constructs have been approached in the past and how to move forward in studying DNA methylation (DNAm), one of the best-characterized epigenetic marks in humans, in a responsible and appropriately nuanced manner. We highlight self-reported racial and ethnic identity as the primary measure in this field, and discuss its implications in DNAm research. Racial and ethnic identity reflects the biological embedding of an individual’s sociocultural experience and environmental exposures in combination with the underlying genetic architecture of the human population (i.e., genetic ancestry). Our integrative framework demonstrates how to examine DNAm in the context of race and ethnicity, while considering both intrinsic factors—including genetic ancestry—and extrinsic factors—including structural and sociocultural environment and developmental niches—when focusing on early-life experience. We reviewed DNAm research in relation to health disparities given its relevance to race and ethnicity as social constructs. Here, we provide recommendations for the study of DNAm addressing racial and ethnic differences, such as explicitly acknowledging the self-reported nature of racial and ethnic identity, empirically examining the effects of genetic variants and accounting for genetic ancestry, and investigating race-related and culturally regulated environmental exposures and experiences.

Associations between the New DNA-Methylation-Based Telomere Length Estimator, the Mediterranean Diet and Genetics in a Spanish Population at High Cardiovascular Risk

“…Considering that linkage disequilibrium and other population characteristics may affect the specific variants most significantly associated in GWASs, it is necessary to conduct studies on multiple populations to assess the level of consistency or heterogeneity in the findings [118]. Similar to the detection of genetic heterogeneity in GWASs, there is also an observed heterogeneity in DNA methylation research based on the ethnic background of the participants [119,120]. Hence, despite the validation and utilization of the DNAmTL estimator in many populations [46][47][48][49][50][51][121][122][123], it is important to obtain specific information related to the Spanish population.…”

The use of race terms in epigenetics research: considerations moving forward

“…The field of epigenetics promises to reveal much about the relationship between social, political, or environmental factors and their influence on health disparities. Epigenetics research has the potential to improve our understanding of how chronic stress, nutritional status, and socio-political structures such as structural racism and environmental racism can influence the health of individuals and impact health across generations ( Breton et al, 2021 ; Salas et al, 2021 ; Chan et al, 2023 ). Epigenetic research is already examining the influence of nutritional status on the epigenome ( Ideraabdullah and Zeisel, 2018 ; Gomez-Verjan et al, 2020 ), the links between DNA methylation and higher incidence rates of chronic pain in African Americans ( Aroke et al, 2019 ), and epigenetic alterations associated with racial trauma ( McDade et al, 2017 ; Grossi, 2020 ).…”

“…However, the intention here is to prompt researchers to think more critically as they design, plan, and carry out experiments, and that when deciding where to allocate time and resources, funding agencies acknowledge the limitations and implications of oversimplifying the role of race. We and others ( Krieger, 2020 ; Chan et al, 2023 ; Lewis et al, 2023 ; National Academies of Sciences E and Medicine, 2023 ) have put forth reccomendations for carrying out genetic and epigenetic research in the context of socially defined race and health disparities. Our recommendations include: 1.…”