Association of Neighborhood Disadvantage in Childhood With DNA Methylation in Young Adulthood

Importance DNA methylation has been proposed as an epigenetic mechanism by which the childhood neighborhood environment may have implications for the genome that compromise adult health. Objective To ascertain whether childhood neighborhood socioeconomic disadvantage is associated with differences in DNA methylation by age 18 years. Design, Setting, and Participants This longitudinal cohort study analyzed data from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally representative birth cohort of children born between 1994 and 1995 in England and Wales and followed up from age 5 to 18 years. Data analysis was performed from March 15, 2019, to June 30, 2019. Exposures High-resolution neighborhood data (indexing deprivation, dilapidation, disconnection, and dangerousness) collected across childhood. Main Outcomes and Measures DNA methylation in whole blood was drawn at age 18 years. Associations between neighborhood socioeconomic disadvantage and methylation were tested using 3 prespecified approaches: (1) testing probes annotated to candidate genes involved in biological responses to growing up in socioeconomically disadvantaged neighborhoods and investigated in previous epigenetic research (stress reactivity-related and inflammation-related genes), (2) polyepigenetic scores indexing differential methylation in phenotypes associated with growing up in disadvantaged neighborhoods (obesity, inflammation, and smoking), and (3) a theory-free epigenome-wide association study. Results A total of 1619 participants (806 female individuals [50%]) had complete neighborhood and DNA methylation data. Children raised in socioeconomically disadvantaged neighborhoods exhibited differential DNA methylation in genes involved in inflammation (beta = 0.12; 95% CI, 0.06-0.19; P < .001) and smoking (beta = 0.18; 95% CI, 0.11-0.25; P < .001) but not obesity (beta = 0.05; 95% CI, -0.01 to 0.11; P = .12). An epigenome-wide association study identified multiple CpG sites at an arraywide significance level of P < 1.16 x 10(-7) in genes involved in the metabolism of hydrocarbons. Associations between neighborhood disadvantage and methylation were small but robust to family-level socioeconomic factors and to individual-level tobacco smoking. Conclusions and Relevance Children raised in more socioeconomically disadvantaged neighborhoods appeared to enter young adulthood epigenetically distinct from their less disadvantaged peers. This finding suggests that epigenetic regulation may be a mechanism by which the childhood neighborhood environment alters adult health. Question Is childhood neighborhood disadvantage associated with differential DNA methylation? Findings In this cohort study of 1619 children in Great Britain, exposure to neighborhood socioeconomic disadvantage during childhood was associated with differential DNA methylation at age 18 years in genes involved in inflammation, exposure to tobacco smoke, and metabolism of toxic air pollutants. Meaning The study found that children who were raised in socioeconomically disadvantaged neighborhoods appeared to enter young adulthood epigenetically distinct from their more advantaged peers. This cohort study traces the biological responses and associated phenotypes of an upbringing in a socially and economically disadvantaged environment.