Background
Exposure to violence (ETV) or stress may cause asthma through unclear mechanisms.
Methods
Epigenome-wide association study (EWAS) of DNA methylation in nasal epithelium and four ETV or chronic stress measures in 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed measures of ETV or chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Each EWAS was conducted using linear regression, with CpGs as dependent variables and the stress/violence measure as a predictor, adjusting for age, sex, the top five principal components, and SVA latent factors. We then selected the top 100 CpGs (by P-value) associated with each stress/violence measure in EVA-PR and conducted a meta-analysis of the selected CpGs and atopic asthma using data from EVA-PR and two additional cohorts (Project Viva and PIAMA).
Results
In the EWAS of stress/violence in EVA-PR, gun violence was associated with methylation of cg18961589 in (β=0.03, =1.28×10 ), and maternal stress was associated with methylation of cg03402351 in (β=0.04, =1.69×10 ) and cg19064846 in (β=0.03, =3.36×10 ). In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence in EVA-PR, CpGs in and were associated with atopic asthma at FDR- < 0.05.
Conclusions
ETV and chronic stress may increase the risk of atopic asthma through DNA methylation in airway epithelium, though this needs confirmation in future longitudinal studies.