title: An epigenome-wide association study of total serum IgE in Hispanic children.
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.
authors.affiliation: Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Instituto de Salud Carlos III, CIBER de Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Pino-Yanes
authors.affiliation: Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Erick
authors.initials: E
authors.lastname: Forno
authors.affiliation: Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, Mass.
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.affiliation: Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Department of Therapeutic Sciences and Bioengineering, University of California at San Francisco, San Francisco, Calif.
authors.forename: Donglei
authors.initials: D
authors.lastname: Hu
authors.affiliation: Departments of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Weeks
authors.affiliation: Department of Environmental Medicine, Harvard School of Public Health, Boston, Mass.
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.affiliation: Behavioral Sciences Research Institute and Department of Pediatrics, University of Puerto Rico, San Juan, Puerto Rico.
authors.forename: Edna
authors.initials: E
authors.lastname: Acosta-Perez
authors.affiliation: Department of Therapeutic Sciences and Bioengineering, University of California at San Francisco, San Francisco, Calif.
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.affiliation: Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Yueh-Ying
authors.initials: YY
authors.lastname: Han
authors.affiliation: Division of Pediatric Pulmonary Medicine, Allergy, and Immunology, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh, Pittsburgh, Pa.
authors.forename: Nadia
authors.initials: N
authors.lastname: Boutaoui
authors.affiliation: Université du Québec à Chicoutimi, Saguenay, Quebec, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Laprise
authors.affiliation: Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom.
authors.forename: Gwyneth A
authors.initials: GA
authors.lastname: Davies
authors.affiliation: Institute of Life Science, Swansea University Medical School, Swansea, United Kingdom.
authors.forename: Julian M
authors.initials: JM
authors.lastname: Hopkin
authors.affiliation: National Heart and Lung Institute, Imperial College, London, United Kingdom.
authors.forename: Miriam F
authors.initials: MF
authors.lastname: Moffatt
authors.affiliation: National Heart and Lung Institute, Imperial College, London, United Kingdom.
authors.forename: William O C M
authors.initials: WOCM
authors.lastname: Cookson
authors.affiliation: Behavioral Sciences Research Institute and Department of Pediatrics, University of Puerto Rico, San Juan, Puerto Rico.
authors.forename: Glorisa
authors.initials: G
authors.lastname: Canino
authors.affiliation: Department of Therapeutic Sciences and Bioengineering, University of California at San Francisco, San Francisco, Calif.
authors.forename: Esteban G
authors.initials: EG
authors.lastname: Burchard
authors.affiliation: 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.
authors.forename: Juan C
authors.initials: JC
authors.lastname: Celedón
mesh_terms: D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D002648:Child; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D055815:Young Adult
chemical_list: D007073:Immunoglobulin E
keywords: Epigenome-wide association study; Hispanic; children; total IgE