Nasal Epigenome-Wide Association Study of Respiratory and Allergic Biomarkers in Mexican American Young Adults
Abstract
Background: Mexican Americans have low asthma prevalence, but they experience a disproportionate clinical asthma burden. Nasal DNA methylation (DNAm) is a biomarker of airway diseases, but its relevance in young adult Mexican Americans and links to air pollution are underexplored. Objective: To identify nasal DNAm markers associated with asthma, allergic sensitization, fractional exhaled nitric oxide (FeNO), and lung function and evaluate associations with air pollution. Methods: We tested associations between nasal DNAm at 804,220 CpGs (EPICv2) and respiratory outcomes in 354 young adults from CHAMACOS (age 22) and evaluated replication in 540 adolescents from Project Viva (age 13). Epigenome-wide association studies were adjusted for confounders, and significance was declared at a false discovery rate (FDR)<0.05. Significant CpGs were evaluated for association with prenatal and past-year PM2.5 and O3 exposures, and with gene expression and genetic variation (in silico). We examined differentially methylated regions (DMRs), gene-set enrichments, and epigenetic aging. Results: We identified 49 CpGs associated with FeNO and 557 DMRs across multiple respiratory outcomes (FDR<0.05). Twenty-six CpGs and 103 DMRs associated with FeNO, asthma, and FEV1/FVC were replicated (e.g., LRRFIP1, PCSK6, EPX, IL13). Ten FeNO-related CpGs were associated with PM2.5 and/or O3 exposures (p<0.05) and 15 CpGs with nasal epithelial expression. We found enrichment for associations with respiratory/allergic biomarkers, obesity, smoking, longevity, asthma-related pathways (PI3K-AKT, TNF-, IL-2), inflammatory transcription factors, and candidate asthma drugs. FeNO was associated with greater epigenetic aging acceleration ({beta}=0.3, p=0.008). Conclusions: We identified nasal DNAm markers implicated in airway epithelial integrity and immune response predominantly associated with FeNO.
Related
- Noninvasive respiratory support for adult patients with acute respiratory failure: an official American Thoracic Society Clinical Practice Guideline
- Occupational endotoxin exposure, DNA methylation changes, and immune-cell remodeling: an epigenome-wide association study in two cohorts
- Posttraumatic Stress Disorder Epigenome-Wide Association Studies in the Million Veteran Program
- Occupational Respiratory and Cutaneous Allergic Diseases in Hairdressers: A Two-center Study
- Association between tobacco & nicotine product use and allergic rhinitis: a cross-sectional study
BibTeX
@misc{perezgarcia2026nasal,
title = {{Nasal Epigenome-Wide Association Study of Respiratory and Allergic Biomarkers in Mexican American Young Adults}},
author = {Javier Perez-Garcia and Robert B. Gunier and Brenda Eskenazi and John Balmes and Katherine Kogut and Weihong Guo and Sheryl L Rifas-Shiman and Marie-France Hivert and Emily Oken and Diane R. Gold and Stephanie Holm and Nina Holland and Andres Cardenas},
howpublished = {medRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.27.26366640},
url = {https://www.medrxiv.org/content/10.64898/2026.10.27.26366640v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Nasal Epigenome-Wide Association Study of Respiratory and Allergic Biomarkers in Mexican American Young Adults
AU - Javier Perez-Garcia
AU - Robert B. Gunier
AU - Brenda Eskenazi
AU - John Balmes
AU - Katherine Kogut
AU - Weihong Guo
AU - Sheryl L Rifas-Shiman
AU - Marie-France Hivert
AU - Emily Oken
AU - Diane R. Gold
AU - Stephanie Holm
AU - Nina Holland
AU - Andres Cardenas
PY - 2026
DA - 2026/10/27
PB - medRxiv
DO - 10.64898/2026.10.27.26366640
UR - https://www.medrxiv.org/content/10.64898/2026.10.27.26366640v1
AB - Background: Mexican Americans have low asthma prevalence, but they experience a disproportionate clinical asthma burden. Nasal DNA methylation (DNAm) is a biomarker of airway diseases, but its relevance in young adult Mexican Americans and links to air pollution are underexplored. Objective: To identify nasal DNAm markers associated with asthma, allergic sensitization, fractional exhaled nitric oxide (FeNO), and lung function and evaluate associations with air pollution. Methods: We tested associations between nasal DNAm at 804,220 CpGs (EPICv2) and respiratory outcomes in 354 young adults from CHAMACOS (age 22) and evaluated replication in 540 adolescents from Project Viva (age 13). Epigenome-wide association studies were adjusted for confounders, and significance was declared at a false discovery rate (FDR)<0.05. Significant CpGs were evaluated for association with prenatal and past-year PM2.5 and O3 exposures, and with gene expression and genetic variation (in silico). We examined differentially methylated regions (DMRs), gene-set enrichments, and epigenetic aging. Results: We identified 49 CpGs associated with FeNO and 557 DMRs across multiple respiratory outcomes (FDR<0.05). Twenty-six CpGs and 103 DMRs associated with FeNO, asthma, and FEV1/FVC were replicated (e.g., LRRFIP1, PCSK6, EPX, IL13). Ten FeNO-related CpGs were associated with PM2.5 and/or O3 exposures (p<0.05) and 15 CpGs with nasal epithelial expression. We found enrichment for associations with respiratory/allergic biomarkers, obesity, smoking, longevity, asthma-related pathways (PI3K-AKT, TNF-, IL-2), inflammatory transcription factors, and candidate asthma drugs. FeNO was associated with greater epigenetic aging acceleration ({beta}=0.3, p=0.008). Conclusions: We identified nasal DNAm markers implicated in airway epithelial integrity and immune response predominantly associated with FeNO.
ER -