An epigenome-wide association study of total serum immunoglobulin E in Hispanic children

Publication date: Available online 6 January 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Wei Chen, Ting Wang, Maria Pino-Yanes, Erick Forno, Liming Liang, Qi Yan, Donglei Hu, Daniel E. Weeks, Andrea Baccarelli, Edna Acosta-Perez, Celeste Eng, Yueh-Ying Han, Nadia Boutaoui, Catherine Laprise, Gwyneth A. Davies, Julian M. Hopkin, Miriam F. Moffatt, William O.C.M. Cookson, Glorisa Canino, Esteban G. Burchard, Juan C. Celedón
BackgroundTotal immunoglobulin E (IgE) is a therapeutic target in allergic diseases. DNA methylation in white blood cells (WBCs) was associated with total IgE in an epigenome-wide association study (EWAS) of Caucasians. Whether DNA methylation of eosinophils explains those findings is insufficiently understood.MethodsWe tested for association between genome-wide DNA methylation in WBCs and total IgE in two 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, n = 573). Whole-genome methylation of DNA from WBCs was measured using the Illumina Infinium HumanMethylation450 BeadChip. Total IgE was measured using the UniCAP 100 system. In PR-GOAL, WBC types (i.e. neutrophils, eosinophils, basophils, lymphocytes, and monocytes) in peripheral blood were measured using Coulter-Counter techniques. In GALA II, WBC types were imputed. Multivariable linear regression was used for the analysis of DNA methylation and total IgE, which was first conducted separately for each cohort, and then combining results from the two cohorts in a meta-analysis.ResultsCpG sites in multiple genes, including novel findings and results previously reported in Caucasians, were significantly associated with total IgE. However, adjustment for WBC types resulted in markedly fewer significant sites. Top findings from this adjusted meta-analysis were in genes ZFPM1 (P=1.5×10^-12), ACOT7 (P=2.5×10^-11), and MND1 (P=1.4×10^-9).ConclusionsIn an EWAS adjusted for WBC types (including eosinophils), methylation changes in genes enriched in pathways relevant to asthma and immune responses were associated with total IgE among Hispanic children.

Teaser

In an EWAS adjusted for WBC types, few DNA methylation changes were significantly associated with total IgE among Hispanic children. Future EWAS of total IgE should account for DNA methylation of WBC types, particularly eosinophils.


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