Cheng Peng1, Andres Cardenas2, Sheryl L Rifas-Shiman2, Marie-France Hivert3, Diane R Gold4, Thomas A Platts-Mills5, Xihong Lin6, Emily Oken2, Lydiana Avila7, Juan C Celedón8, Scott T Weiss9, Andrea A Baccarelli10, Augusto A Litonjua11, Dawn L DeMeo11. 1. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. Electronic address: recpe@channing.harvard.edu. 2. Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Mass. 3. Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, Mass; Diabetes Unit, Massachusetts General Hospital, Boston, Mass. 4. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Mass. 5. Division of Allergy and Clinical Immunology, University of Virginia School of Medicine, Charlottesville, Va. 6. Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, Mass. 7. Department of Pediatrics, Hospital Nacional de Niños, San José, Costa Rica. 8. Division of Pediatric Pulmonary Medicine, UPMC Children's Hospital of Pittsburgh, University of Pittsburgh, Pittsburgh, Pa. 9. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass. 10. Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY. 11. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass; Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass.
Abstract
BACKGROUND: Epigenetic clocks have been suggested to capture one feature of the complexity between aging and the epigenome. However, little is known about the epigenetic clock in childhood allergy and asthma. OBJECTIVE: We sought to examine associations of DNA methylation age (DNAmAge) and epigenetic age acceleration with childhood allergy and asthma. METHODS: We calculated DNAmAge and age acceleration at birth, early childhood, and midchildhood based on the IlluminaHumanMethylation450BeadChip in Project Viva. We evaluated epigenetic clock associations with allergy and asthma using covariate-adjusted linear and logistic regressions. We attempted to replicate our findings in the Genetics of Asthma in Costa Rica Study. RESULTS: At midchildhood (mean age, 7.8 years) in Project Viva, DNAmAge and age acceleration were cross-sectionally associated with greater total serum IgE levels and greater odds of atopic sensitization. Every 1-year increase in intrinsic epigenetic age acceleration was associated with a 1.22 (95% CI, 1.07-1.39), 1.17 (95% CI, 1.03-1.34), and 1.29 (95% CI, 1.12-1.49) greater odds of atopic sensitization and environmental and food allergen sensitization. DNAmAge and extrinsic epigenetic age acceleration were also cross-sectionally associated with current asthma at midchildhood. DNAmAge and age acceleration at birth and early childhood were not associated with midchildhood allergy or asthma. The midchildhood association between age acceleration and atopic sensitization were replicated in an independent data set. CONCLUSIONS: Because the epigenetic clock might reflect immune and developmental components of biological aging, our study suggests pathways through which molecular epigenetic mechanisms of immunity, development, and maturation can interact along the age axis and associate with childhood allergy and asthma by midchildhood.
BACKGROUND: Epigenetic clocks have been suggested to capture one feature of the complexity between aging and the epigenome. However, little is known about the epigenetic clock in childhood allergy and asthma. OBJECTIVE: We sought to examine associations of DNA methylation age (DNAmAge) and epigenetic age acceleration with childhood allergy and asthma. METHODS: We calculated DNAmAge and age acceleration at birth, early childhood, and midchildhood based on the IlluminaHumanMethylation450BeadChip in Project Viva. We evaluated epigenetic clock associations with allergy and asthma using covariate-adjusted linear and logistic regressions. We attempted to replicate our findings in the Genetics of Asthma in Costa Rica Study. RESULTS: At midchildhood (mean age, 7.8 years) in Project Viva, DNAmAge and age acceleration were cross-sectionally associated with greater total serum IgE levels and greater odds of atopic sensitization. Every 1-year increase in intrinsic epigenetic age acceleration was associated with a 1.22 (95% CI, 1.07-1.39), 1.17 (95% CI, 1.03-1.34), and 1.29 (95% CI, 1.12-1.49) greater odds of atopic sensitization and environmental and food allergen sensitization. DNAmAge and extrinsic epigenetic age acceleration were also cross-sectionally associated with current asthma at midchildhood. DNAmAge and age acceleration at birth and early childhood were not associated with midchildhood allergy or asthma. The midchildhood association between age acceleration and atopic sensitization were replicated in an independent data set. CONCLUSIONS: Because the epigenetic clock might reflect immune and developmental components of biological aging, our study suggests pathways through which molecular epigenetic mechanisms of immunity, development, and maturation can interact along the age axis and associate with childhood allergy and asthma by midchildhood.
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