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DNA methylation at birth is associated with childhood serum immunoglobulin E levels

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
2516-8657
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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Han, Luhang
cfeafb0c-3b49-41ab-b05f-9cccf7573036
Kaushal, Akhilesh
a7742b05-148f-411e-bd3d-c2c29ecdcfef
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
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Wen, Hui-Ju
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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).

Record type: Article

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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Accepted/In Press date: 25 November 2020
e-pub ahead of print date: 5 April 2021
Additional Information: .
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
ORCID for John Holloway: ORCID iD orcid.org/0000-0001-9998-0464

Catalogue record

Date deposited: 14 Dec 2020 17:32
Last modified: 26 Nov 2021 02:40

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Contributors

Author: Luhang Han
Author: Akhilesh Kaushal
Author: Hongmei Zhang
Author: Jiasong Duan
Author: John Holloway ORCID iD
Author: Wilfried Karmaus
Author: Pratik Banerjee
Author: Shih-Fen Tsai
Author: Hui-Ju Wen
Author: Syed Arshad
Author: Shu-Li Wang

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