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

A polygenic score for age-at-first-birth predicts disinhibition.

BACKGROUND: A recent genome-wide association study identified molecular-genetic associations with age-at-first-birth. However, the meaning of these genetic discoveries is unclear. Drawing on evidence linking early pregnancy with disinhibitory behavior, we tested the hypothesis that genetic discoveries for age-at-first-birth predict disinhibition. METHODS: We included participants with genotype data from the two-decade-long Environmental Risk (E-Risk) Study (N = 1,999) and the four-decade-long Dunedin Study (N = 918). We calculated a genome-wide polygenic score for age-at-first-birth and tested whether it was associated with a range of disinhibitory outcomes across the life course, including low childhood self-control; risk for externalizing psychopathology; officially recorded criminal offending; substance dependence; informant reports of disinhibitory problems; and number of lifetime sexual partners. We further tested whether associations were attributable to accelerated pubertal maturation. RESULTS: In both cohorts, the age-at-first-birth polygenic score predicted low childhood self-control, externalizing psychopathology, officially recorded criminal offending, substance dependence, and number of sexual partners. Associations were modest, but robust across replication. Childhood disinhibition partly mediated associations between the polygenic score and reproductive behaviors. In contrast, associations were not attributable to accelerated pubertal timing. CONCLUSIONS: Genomic discoveries for age-at-first-birth are about more than reproductive biology: They provide insight into the disinhibitory traits and behaviors that accompany early parenthood. Age-at-first-birth is a useful proxy phenotype for researchers interested in disinhibition. Further, interventions that improve self-regulation abilities may benefit young parents and their children.