biostudies-literatureLi YNIAID NIH HHSMassachusetts General Hospital Department of Emergency Medicine Fellowship/Eleanor and Miles Shore Faculty Development Awards Program Harvard University William F. Milton FundU.S. Department of Health & Human Services | National Institutes of Health (NIH)Harvard UniversityU.S. Department of Health &amp; Human Services | National Institutes of HealthNIH HHS3556https://www.ebi.ac.uk/biostudies/studies/S-EPMC11997043biostudies-literatureUnknown16(1)Infants with severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) face increased risks of respiratory diseases in childhood. We conduct epigenome-wide association studies in a multi-ethnic cohort of these infants. We identify 61 differentially methylated regions in infant blood (<1 year of age) associated with recurrent wheezing by age 3 (170 cases, 318 non-cases) and/or asthma by age 6 (112 cases, 394 non-cases). These differentially methylated regions are enriched in the enhancers of peripheral blood neutrophils. Several differentially methylated regions exhibit interaction with rhinovirus infection and/or specific blood cell types. In the same blood samples, circulating levels of 104 proteins correlate with the differentially methylated regions, and many proteins show phNature communicationsEpigenomic and proteomic analyses provide insights into early-life immune regulation and asthma development in infants.PMC11997043R01 AI134940R01 AI-137091R01 AI-114552R01 AI-148338Harvard University William F. Milton FundR01 AI127507UG3 OD023253K01 AI-153558UG3/UH3 OD-023253U01 AI087881R01 AI114552R01 AI148338R01 AI-134940R01 AI137091U01 AI-087881K01 AI153558R01 AI-127507Li YZhu ZEspinola JALiang LCamargo CAHasegawa KfalseEpigenomic and proteomic analyses provide insights into early-life immune regulation and asthma development in infants.Infants with severe bronchiolitis (i.e., bronchiolitis requiring hospitalization) face increased risks of respiratory diseases in childhood. We conduct epigenome-wide association studies in a multi-ethnic cohort of these infants. We identify 61 differentially methylated regions in infant blood (<1 year of age) associated with recurrent wheezing by age 3 (170 cases, 318 non-cases) and/or asthma by age 6 (112 cases, 394 non-cases). These differentially methylated regions are enriched in the enhancers of peripheral blood neutrophils. Several differentially methylated regions exhibit interaction with rhinovirus infection and/or specific blood cell types. In the same blood samples, circulating levels of 104 proteins correlate with the differentially methylated regions, and many proteins show ph2025-01-01T00:00:00Z2025 Apr2025-07-14T03:02:43.085Z2025-07-14T03:02:43.085ZS-EPMC119970434022923410.1038/s41467-025-57288-6