Dataset Information

Epigenome-wide meta-analysis of DNA methylation and childhood asthma.

ABSTRACT:

Background

Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis.

Objective

We sought to identify differential DNA methylation in newborns and children related to childhood asthma.

Methods

Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in blood measured either in newborns, in prospective analyses, or cross-sectionally in school-aged children. We also identified differentially methylated regions.

Results

In newborns (8 cohorts, 668 cases), 9 CpGs (and 35 regions) were differentially methylated (epigenome-wide significance, false discovery rate < 0.05) in relation to asthma development. In a cross-sectional meta-analysis of asthma and methylation in children (9 cohorts, 631 cases), we identified 179 CpGs (false discovery rate < 0.05) and 36 differentially methylated regions. In replication studies of methylation in other tissues, most of the 179 CpGs discovered in blood replicated, despite smaller sample sizes, in studies of nasal respiratory epithelium or eosinophils. Pathway analyses highlighted enrichment for asthma-relevant immune processes and overlap in pathways enriched both in newborns and children. Gene expression correlated with methylation at most loci. Functional annotation supports a regulatory effect on gene expression at many asthma-associated CpGs. Several implicated genes are targets for approved or experimental drugs, including IL5RA and KCNH2.

Conclusion

Novel loci differentially methylated in newborns represent potential biomarkers of risk of asthma by school age. Cross-sectional associations in children can reflect both risk for and effects of disease. Asthma-related differential methylation in blood in children was substantially replicated in eosinophils and respiratory epithelium.

SUBMITTER: Reese SE

PROVIDER: S-EPMC6556405 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Publications

Epigenome-wide meta-analysis of DNA methylation and childhood asthma.

Reese Sarah E SE Xu Cheng-Jian CJ den Dekker Herman T HT Lee Mi Kyeong MK Sikdar Sinjini S Ruiz-Arenas Carlos C Merid Simon K SK Rezwan Faisal I FI Page Christian M CM Ullemar Vilhelmina V Melton Phillip E PE Oh Sam S SS Yang Ivana V IV Burrows Kimberley K Söderhäll Cilla C Jima Dereje D DD Gao Lu L Arathimos Ryan R Küpers Leanne K LK Wielscher Matthias M Rzehak Peter P Lahti Jari J Laprise Catherine C Madore Anne-Marie AM Ward James J Bennett Brian D BD Wang Tianyuan T Bell Douglas A DA Vonk Judith M JM Håberg Siri E SE Zhao Shanshan S Karlsson Robert R Hollams Elysia E Hu Donglei D Richards Adam J AJ Bergström Anna A Sharp Gemma C GC Felix Janine F JF Bustamante Mariona M Gruzieva Olena O Maguire Rachel L RL Gilliland Frank F Baïz Nour N Nohr Ellen A EA Corpeleijn Eva E Sebert Sylvain S Karmaus Wilfried W Grote Veit V Kajantie Eero E Magnus Maria C MC Örtqvist Anne K AK Eng Celeste C Liu Andrew H AH Kull Inger I Jaddoe Vincent W V VWV Sunyer Jordi J Kere Juha J Hoyo Cathrine C Annesi-Maesano Isabella I Arshad Syed Hasan SH Koletzko Berthold B Brunekreef Bert B Binder Elisabeth B EB Räikkönen Katri K Reischl Eva E Holloway John W JW Jarvelin Marjo-Riitta MR Snieder Harold H Kazmi Nabila N Breton Carrie V CV Murphy Susan K SK Pershagen Göran G Anto Josep Maria JM Relton Caroline L CL Schwartz David A DA Burchard Esteban G EG Huang Rae-Chi RC Nystad Wenche W Almqvist Catarina C Henderson A John AJ Melén Erik E Duijts Liesbeth L Koppelman Gerard H GH London Stephanie J SJ

The Journal of allergy and clinical immunology 20181221 6

<h4>Background</h4>Epigenetic mechanisms, including methylation, can contribute to childhood asthma. Identifying DNA methylation profiles in asthmatic patients can inform disease pathogenesis.<h4>Objective</h4>We sought to identify differential DNA methylation in newborns and children related to childhood asthma.<h4>Methods</h4>Within the Pregnancy And Childhood Epigenetics consortium, we performed epigenome-wide meta-analyses of school-age asthma in relation to CpG methylation (Illumina450K) in ...[more]

PMID: 30579849

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Project description:BackgroundPrenatal exposure to air pollution has been associated with childhood respiratory disease and other adverse outcomes. Epigenetics is a suggested link between exposures and health outcomes.ObjectivesWe aimed to investigate associations between prenatal exposure to particulate matter (PM) with diameter [Formula: see text] ([Formula: see text]) or [Formula: see text] ([Formula: see text]) and DNA methylation in newborns and children.MethodsWe meta-analyzed associations between exposure to [Formula: see text] ([Formula: see text]) and [Formula: see text] ([Formula: see text]) at maternal home addresses during pregnancy and newborn DNA methylation assessed by Illumina Infinium HumanMethylation450K BeadChip in nine European and American studies, with replication in 688 independent newborns and look-up analyses in 2,118 older children. We used two approaches, one focusing on single cytosine-phosphate-guanine (CpG) sites and another on differentially methylated regions (DMRs). We also related PM exposures to blood mRNA expression.ResultsSix CpGs were significantly associated [false discovery rate (FDR) [Formula: see text]] with prenatal [Formula: see text] and 14 with [Formula: see text] exposure. Two of the [Formula: see text] CpGs mapped to FAM13A (cg00905156) and NOTCH4 (cg06849931) previously associated with lung function and asthma. Although these associations did not replicate in the smaller newborn sample, both CpGs were significant ([Formula: see text]) in 7- to 9-y-olds. For cg06849931, however, the direction of the association was inconsistent. Concurrent [Formula: see text] exposure was associated with a significantly higher NOTCH4 expression at age 16 y. We also identified several DMRs associated with either prenatal [Formula: see text] and or [Formula: see text] exposure, of which two [Formula: see text] DMRs, including H19 and MARCH11, replicated in newborns.ConclusionsSeveral differentially methylated CpGs and DMRs associated with prenatal PM exposure were identified in newborns, with annotation to genes previously implicated in lung-related outcomes. https://doi.org/10.1289/EHP4522.

Dataset Information

Epigenome-wide meta-analysis of DNA methylation and childhood asthma.

Background

Objective

Methods

Results

Conclusion

Publications

Epigenome-wide meta-analysis of DNA methylation and childhood asthma.

Similar Datasets

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