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

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  • Aaron Reuben
  • Karen Sugden
  • Louise Arseneault
  • David L Corcoran
  • Andrea Danese
  • Helen L Fisher
  • Terrie E Moffitt
  • Joanne B Newbury
  • Candice Odgers
  • Joey Prinz
  • Line J H Rasmussen
  • Ben Williams
  • Jonathan Mill
  • Avshalom Caspi
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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.

Original languageEnglish
Article numbere206095
JournalJAMA network open
Volume3
Issue number6
ISSN2574-3805
DOIs
Publication statusPublished - 1 Jun 2020

ID: 59973015