Qi Yan1, Erick Forno1, Andres Cardenas2,3, Cancan Qi4,5, Yueh-Ying Han1, Edna Acosta-Pérez6, Soyeon Kim1, Rong Zhang1,7, Nadia Boutaoui1, Glorisa Canino6, Judith M Vonk5,8, Cheng-Jian Xu4,5, Wei Chen1, Anna Marsland9, Emily Oken3, Diane R Gold10,11, Gerard H Koppelman4,5, Juan C Celedón1. 1. Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 2. Division of Environmental Health Sciences, University of California, Berkeley, California, USA. 3. Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Massachusetts, USA. 4. Department of Pediatric Pulmonology and Pediatric Allergy, University Medical Center Groningen, Beatrix Children's Hospital, University of Groningen, Groningen, The Netherlands. 5. University Medical Center Groningen, GRIAC Research Institute, University of Groningen, Groningen, The Netherlands. 6. Behavioral Sciences Research Institute, University of Puerto Rico, San Juan, Puerto Rico. 7. Department of Statistics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 8. Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 9. Department of Psychology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. 10. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. 11. Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
Abstract
BACKGROUND: Exposure to violence (ETV) or chronic stress may influence asthma through unclear mechanisms. METHODS: Epigenome-wide association study (EWAS) of ETV or chronic stress measures and DNA methylation in nasal epithelium from 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed four measures of ETV and 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: Three CpGs (in SNN, PTPRN2, and LINC01164) were associated with maternal perceived stress or gun violence (p = 1.28-3.36 × 10-7 ), but not with atopic asthma, in EVA-PR. In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence measures in EVA-PR, 12 CpGs (in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4, and ANAPC13) were associated with atopic asthma at FDR-p < .05. CONCLUSIONS: Pending confirmation in longitudinal studies, our findings suggest that nasal epithelial methylation markers associated with measures of ETV and chronic stress may be linked to atopic asthma in children and adolescents.
BACKGROUND: Exposure to violence (ETV) or chronic stress may influence asthma through unclear mechanisms. METHODS: Epigenome-wide association study (EWAS) of ETV or chronic stress measures and DNA methylation in nasal epithelium from 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed four measures of ETV and 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: Three CpGs (in SNN, PTPRN2, and LINC01164) were associated with maternal perceived stress or gun violence (p = 1.28-3.36 × 10-7 ), but not with atopic asthma, in EVA-PR. In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence measures in EVA-PR, 12 CpGs (in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4, and ANAPC13) were associated with atopic asthma at FDR-p < .05. CONCLUSIONS: Pending confirmation in longitudinal studies, our findings suggest that nasal epithelial methylation markers associated with measures of ETV and chronic stress may be linked to atopic asthma in children and adolescents.
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