How are social determinants of health integrated into epigenetic research? A systematic review

Objective: We systematically review the literature on social epigenetics, examining how empirical research to date has conceptualized and operationalized social determinants of health (SDOH). Methods: Using comprehensive search procedures, we identified studies that consider the impact of SDOH on DNA methylation (DNAm), the most common measure of epigenetic change in research on human adult populations. We analyzed the studies to determine: 1) which populations and environments have been investigated in the literature; 2) how SDOH are defined and operationalized; 3) which SDOH have been linked to DNAm; and 4) what lessons from the SDOH literature can be better integrated into future studies exploring the social determinants of health and epigenetic outcomes. Results: We identified 67 studies, with 39 to 8397 participants. The SDOH most commonly considered were early life socioeconomic exposures and early life trauma or mental health. Our review highlights four broad challenges: a) high dependence on convenience sampling, b) limited racial/ethnic, and geographic diversity in sampling frames, c) overreliance on individual sociodemographic characteristics as proxies for broader stratification processes, and d) a focus on downstream social determinants of health and individualized experiences with social stressors. Conclusions: Future social epigenetics research should prioritize larger, more diverse and representative population-based samples and employ the SDOH framework to better inform the conceptualization of research questions and interpretation of findings. In particular, the simplified depiction of race/ethnicity, gender, and socioeconomic status as individual-level characteristics should be updated with an explicit acknowledgement that these characteristics are more accurately interpreted as cues used by society to differentiate subpopulations. Social epigenetics research can then more clearly elucidate the biological consequences of these social exposures for patterns of gene expression, subsequent disease etiology, and health inequities.