DNA methylation at birth is associated with childhood serum immunoglobulin E levels
DNA methylation at birth is associated with childhood serum immunoglobulin E levels
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.
DNA methylation, Immunoglobulin E, Isle of Wight cohort, Taiwan cohort, childhood, cord blood, epigenetic, longitudinal
Han, Luhang
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Kaushal, Akhilesh
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Zhang, Hongmei
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Perunthadambil Kadalayil, Latha
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Duan, Jiasong
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Holloway, John
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Karmaus, Wilfried
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Banerjee, Pratik
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Tsai, Shih-Fen
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Wen, Hui-Ju
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Arshad, Syed
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Wang, Shu-Li
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5 April 2021
Han, Luhang
cfeafb0c-3b49-41ab-b05f-9cccf7573036
Kaushal, Akhilesh
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Zhang, Hongmei
9f774048-54d6-4321-a252-3887b2c76db0
Perunthadambil Kadalayil, Latha
e620b801-844a-45d9-acaf-e0a58acd7cf2
Duan, Jiasong
c8f2e3fe-413f-4cd5-9a1c-28830d36ef04
Holloway, John
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Karmaus, Wilfried
281d0e53-6b5d-4d38-9732-3981b07cd853
Banerjee, Pratik
5edf3b7a-75b1-4c9d-af69-fab96f273166
Tsai, Shih-Fen
8f9db07c-e9bc-49fb-83ac-7a0a806d3218
Wen, Hui-Ju
8fde4fc5-c901-4877-a1fd-d4fdc5a270ad
Arshad, Syed
917e246d-2e60-472f-8d30-94b01ef28958
Wang, Shu-Li
7ca21a8d-2516-4c83-81e5-3da6eccca879
Han, Luhang, Kaushal, Akhilesh, Zhang, Hongmei, Perunthadambil Kadalayil, Latha, Duan, Jiasong, Holloway, John, Karmaus, Wilfried, Banerjee, Pratik, Tsai, Shih-Fen, Wen, Hui-Ju, Arshad, Syed and Wang, Shu-Li
(2021)
DNA methylation at birth is associated with childhood serum immunoglobulin E levels.
Epigenetics Insights, 14.
(doi:10.1177/25168657211008108).
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.
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Manuscript final 201117_
- Accepted Manuscript
More information
Accepted/In Press date: 25 November 2020
e-pub ahead of print date: 5 April 2021
Published date: 5 April 2021
Additional Information:
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).
Publisher Copyright:
© The Author(s) 2021.
Keywords:
DNA methylation, Immunoglobulin E, Isle of Wight cohort, Taiwan cohort, childhood, cord blood, epigenetic, longitudinal
Identifiers
Local EPrints ID: 445528
URI: http://eprints.soton.ac.uk/id/eprint/445528
ISSN: 2516-8657
PURE UUID: ef91fe16-e219-49cf-8d99-3919a9495696
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Date deposited: 14 Dec 2020 17:32
Last modified: 17 Mar 2024 02:45
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Contributors
Author:
Luhang Han
Author:
Akhilesh Kaushal
Author:
Hongmei Zhang
Author:
Jiasong Duan
Author:
Wilfried Karmaus
Author:
Pratik Banerjee
Author:
Shih-Fen Tsai
Author:
Hui-Ju Wen
Author:
Shu-Li Wang
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