Wei Chen1, Ting Wang1, Maria Pino-Yanes2, Erick Forno1, Liming Liang3, Qi Yan1, Donglei Hu4, Daniel E Weeks5, Andrea Baccarelli6, Edna Acosta-Perez7, Celeste Eng4, Yueh-Ying Han1, Nadia Boutaoui1, Catherine Laprise8, Gwyneth A Davies9, Julian M Hopkin9, Miriam F Moffatt10, William O C M Cookson10, Glorisa Canino7, Esteban G Burchard4, Juan C Celedón11. 1. Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pa. 2. Instituto de Salud Carlos III, CIBER de Enfermedades Respiratorias, Madrid, Spain. 3. Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, Mass. 4. Department of Therapeutic Sciences and Bioengineering, University of California at San Francisco, San Francisco, Calif. 5. Departments of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa. 6. Department of Environmental Medicine, Harvard School of Public Health, Boston, Mass. 7. Behavioral Sciences Research Institute and Department of Pediatrics, University of Puerto Rico, San Juan, Puerto Rico. 8. Université du Québec à Chicoutimi, Saguenay, Quebec, Canada. 9. Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom. 10. National Heart and Lung Institute, Imperial College, London, United Kingdom. 11. Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pa. Electronic address: juan.celedon@chp.edu.
Abstract
BACKGROUND: Total IgE is a therapeutic target in patients with allergic diseases. DNA methylation in white blood cells (WBCs) was associated with total IgE levels in an epigenome-wide association study of white subjects. Whether DNA methylation of eosinophils explains these findings is insufficiently understood. METHODS: We tested for association between genome-wide DNA methylation in WBCs and total IgE levels in 2 studies of Hispanic children: the Puerto Rico Genetics of Asthma and Lifestyle Study (PR-GOAL; n = 306) and the Genes-environments and Admixture in Latino Americans (GALA II) study (n = 573). Whole-genome methylation of DNA from WBCs was measured by using the Illumina Infinium HumanMethylation450 BeadChip. Total IgE levels were measured by using the UniCAP 100 system. In PR-GOAL WBC types (ie, neutrophils, eosinophils, basophils, lymphocytes, and monocytes) in peripheral blood were measured by using Coulter Counter techniques. In the GALA II study WBC types were imputed. Multivariable linear regression was used for the analysis of DNA methylation and total IgE levels, which was first conducted separately for each cohort, and then results from the 2 cohorts were combined in a meta-analysis. RESULTS: CpG sites in multiple genes, including novel findings and results previously reported in white subjects, were significantly associated with total IgE levels. However, adjustment for WBC types resulted in markedly fewer significant sites. Top findings from this adjusted meta-analysis were in the genes ZFPM1 (P = 1.5 × 10-12), ACOT7 (P = 2.5 × 10-11), and MND1 (P = 1.4 × 10-9). CONCLUSIONS: In an epigenome-wide association study adjusted for WBC types (including eosinophils), methylation changes in genes enriched in pathways relevant to asthma and immune responses were associated with total IgE levels among Hispanic children.
BACKGROUND: Total IgE is a therapeutic target in patients with allergic diseases. DNA methylation in white blood cells (WBCs) was associated with total IgE levels in an epigenome-wide association study of white subjects. Whether DNA methylation of eosinophils explains these findings is insufficiently understood. METHODS: We tested for association between genome-wide DNA methylation in WBCs and total IgE levels in 2 studies of Hispanic children: the Puerto Rico Genetics of Asthma and Lifestyle Study (PR-GOAL; n = 306) and the Genes-environments and Admixture in Latino Americans (GALA II) study (n = 573). Whole-genome methylation of DNA from WBCs was measured by using the Illumina Infinium HumanMethylation450 BeadChip. Total IgE levels were measured by using the UniCAP 100 system. In PR-GOAL WBC types (ie, neutrophils, eosinophils, basophils, lymphocytes, and monocytes) in peripheral blood were measured by using Coulter Counter techniques. In the GALA II study WBC types were imputed. Multivariable linear regression was used for the analysis of DNA methylation and total IgE levels, which was first conducted separately for each cohort, and then results from the 2 cohorts were combined in a meta-analysis. RESULTS: CpG sites in multiple genes, including novel findings and results previously reported in white subjects, were significantly associated with total IgE levels. However, adjustment for WBC types resulted in markedly fewer significant sites. Top findings from this adjusted meta-analysis were in the genes ZFPM1 (P = 1.5 × 10-12), ACOT7 (P = 2.5 × 10-11), and MND1 (P = 1.4 × 10-9). CONCLUSIONS: In an epigenome-wide association study adjusted for WBC types (including eosinophils), methylation changes in genes enriched in pathways relevant to asthma and immune responses were associated with total IgE levels among Hispanic children.
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