DNA Methylation at Birth is Associated with Childhood Serum Immunoglobulin E Levels

• Type of Material: Article
• Authors: Luhang Han, University of Memphis; Akhilesh Kaushal, Emory University School of Medicine; Hongmei Zhang, University of Memphis; Latha Kadalayil, University of Southampton, Faculty of Medicine; Jiasong Duan, University of Memphis; John W Holloway, University of Southampton, Faculty of Medicine; Wilfried Karmaus, University of Memphis; Pratik Banerjee, University of Illinois Urbana-Champaign; Shih-Fen Tsai, National Health Research Institutes Taiwan; Hui-Ju Wen, National Health Research Institutes Taiwan; Syed Hasan Arshad, University of Southampton, Faculty of Medicine; Shu-Li Wang, National Health Research Institutes Taiwan
• Language: English
• Date: 2021-01-01
• Publisher: SageJournals
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2021
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1177/25168657211008108
• Title of Journal or Parent Work: Epigenetics Insights
• Volume: 14
• Start Page: 25168657211008108
• End Page: 25168657211008108
• Grant/Funding Information: The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: Funding for the Maternal and Infant Cohort Study in Taiwan was provided by the National Health Research Institutes, Miaoli, Taiwan (Grant No.: EM-105-PP-05), and the Ministry of Science and Technology, Taiwan (MOST104-2314-B-400-001). Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases at National Institutes of Health (NIH), USA, under award numbers R01 AI091905 (PI: Wilfried Karmaus) and R01 AI121226 (MPI: Hongmei Zhang, John Holloway).
• Keywords: epigenetic; Taiwan cohort; longitudinal; Isle of Wight cohort; Immunoglobulin E; childhood; DNA methylation; cord blood
• Research Categories: Health Sciences, Epidemiology; Biology, Biostatistics

Abstract

Immunoglobulin E (IgE) is known to play an important role in allergic diseases. Epigenetic traits acquired due to modification of deoxyribonucleic acid (DNA) methylation (DNAm) in early life may have phenotypic consequences through their role in transcriptional regulation with relevance to the developmental origins of diseases including allergy. However, epigenome-scale studies on the longitudinal association of cord blood DNAm with IgE over time are lacking. Our study aimed to examine the association of DNAm at birth with childhood serum IgE levels during early life. Genome-scale DNAm and total serum IgE measured at birth, 5, 8, and 11 years of children in the Taiwan Maternal and Infant Cohort Study were included in the study in the discovery stage. Linear mixed models were implemented to assess the association between cord blood DNAm at ~310K 5′-cytosine-phosphate-guanine-3′ (CpG) sites with repeated IgE measurements, adjusting for cord blood IgE. Identified statistically significant CpGs (at a false discovery rate, FDR, of 0.05) were further tested in an independent replication cohort, the Isle of Wight (IoW) birth cohort. We mapped replicated CpGs to genes and conducted gene ontology analysis using ToppFun to identify significantly enriched pathways and biological processes of the genes. Cord blood DNAm of 273 CpG sites were significantly (FDR = 0.05) associated with IgE levels longitudinally. Among the identified CpGs available in both cohorts (184 CpGs), 92 CpGs (50%) were replicated in the IoW in terms of consistency in direction of associations between DNA methylation and IgE levels later in life, and 16 of the 92 CpGs showed statistically significant associations (P <.05). Gene ontology analysis identified 4 pathways (FDR = 0.05). The identified 16 CpG sites had the potential to serve as epigenetic markers associated with later IgE production, beneficial to allergic disease prevention and intervention.