Exposure to violence, chronic stress, nasal DNA methylation, and atopic asthma in children.

Exposure to violence (ETV) or stress may cause asthma through unclear mechanisms. 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). In the EWAS of stress/violence in EVA-PR, gun violence was associated with methylation of cg18961589 in LINC01164 (β=0.03, P =1.28×10 -7 ), and maternal stress was associated with methylation of cg03402351 in SNN (β=0.04, P =1.69×10 -7 ) and cg19064846 in PTPRN2 (β=0.03, P =3.36×10 -7 ). In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence in EVA-PR, CpGs in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4 and ANAPC13 were associated with atopic asthma at FDR- P < 0.05. 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.