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

JAMA Netw Open. 2020 Jun 1;3(6):e206095. doi: 10.1001/jamanetworkopen.2020.6095.


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 (β = 0.12; 95% CI, 0.06-0.19; P < .001) and smoking (β = 0.18; 95% CI, 0.11-0.25; P < .001) but not obesity (β = 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 × 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.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Twin Study

MeSH terms

  • Adolescent
  • Air Pollutants / toxicity
  • Child
  • Child, Preschool
  • DNA / blood*
  • DNA Methylation / genetics*
  • England / epidemiology
  • Epigenesis, Genetic / genetics*
  • Female
  • Humans
  • Inflammation / genetics
  • Longitudinal Studies
  • Male
  • Obesity / genetics
  • Obesity / metabolism
  • Outcome Assessment, Health Care
  • Phenotype
  • Residence Characteristics / statistics & numerical data*
  • Smoking / genetics
  • Socioeconomic Factors


  • Air Pollutants
  • DNA