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

Publication ,  Journal Article
Reese, SE; Xu, C-J; den Dekker, HT; Lee, MK; Sikdar, S; Ruiz-Arenas, C; Merid, SK; Rezwan, FI; Page, CM; Ullemar, V; Melton, PE; Oh, SS ...
Published in: J Allergy Clin Immunol
June 2019

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.

Duke Scholars

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Published In

J Allergy Clin Immunol

DOI

EISSN

1097-6825

Publication Date

June 2019

Volume

143

Issue

6

Start / End Page

2062 / 2074

Location

United States

Related Subject Headings

  • Interleukin-5 Receptor alpha Subunit
  • Infant, Newborn
  • Humans
  • Genome-Wide Association Study
  • Epigenome
  • Epigenesis, Genetic
  • ERG1 Potassium Channel
  • DNA Methylation
  • Cross-Sectional Studies
  • CpG Islands
 

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Reese, S. E., Xu, C.-J., den Dekker, H. T., Lee, M. K., Sikdar, S., Ruiz-Arenas, C., … London, S. J. (2019). Epigenome-wide meta-analysis of DNA methylation and childhood asthma. J Allergy Clin Immunol, 143(6), 2062–2074. https://doi.org/10.1016/j.jaci.2018.11.043
Reese, Sarah E., Cheng-Jian Xu, Herman T. den Dekker, Mi Kyeong Lee, Sinjini Sikdar, Carlos Ruiz-Arenas, Simon K. Merid, et al. “Epigenome-wide meta-analysis of DNA methylation and childhood asthma.J Allergy Clin Immunol 143, no. 6 (June 2019): 2062–74. https://doi.org/10.1016/j.jaci.2018.11.043.
Reese SE, Xu C-J, den Dekker HT, Lee MK, Sikdar S, Ruiz-Arenas C, et al. Epigenome-wide meta-analysis of DNA methylation and childhood asthma. J Allergy Clin Immunol. 2019 Jun;143(6):2062–74.
Reese, Sarah E., et al. “Epigenome-wide meta-analysis of DNA methylation and childhood asthma.J Allergy Clin Immunol, vol. 143, no. 6, June 2019, pp. 2062–74. Pubmed, doi:10.1016/j.jaci.2018.11.043.
Reese SE, Xu C-J, den Dekker HT, Lee MK, Sikdar S, Ruiz-Arenas C, Merid SK, Rezwan FI, Page CM, Ullemar V, Melton PE, Oh SS, Yang IV, Burrows K, Söderhäll C, Jima DD, Gao L, Arathimos R, Küpers LK, Wielscher M, Rzehak P, Lahti J, Laprise C, Madore A-M, Ward J, Bennett BD, Wang T, Bell DA, BIOS consortium, Vonk JM, Håberg SE, Zhao S, Karlsson R, Hollams E, Hu D, Richards AJ, Bergström A, Sharp GC, Felix JF, Bustamante M, Gruzieva O, Maguire RL, Gilliland F, Baïz N, Nohr EA, Corpeleijn E, Sebert S, Karmaus W, Grote V, Kajantie E, Magnus MC, Örtqvist AK, Eng C, Liu AH, Kull I, Jaddoe VWV, Sunyer J, Kere J, Hoyo C, Annesi-Maesano I, Arshad SH, Koletzko B, Brunekreef B, Binder EB, Räikkönen K, Reischl E, Holloway JW, Jarvelin M-R, Snieder H, Kazmi N, Breton CV, Murphy SK, Pershagen G, Anto JM, Relton CL, Schwartz DA, Burchard EG, Huang R-C, Nystad W, Almqvist C, Henderson AJ, Melén E, Duijts L, Koppelman GH, London SJ. Epigenome-wide meta-analysis of DNA methylation and childhood asthma. J Allergy Clin Immunol. 2019 Jun;143(6):2062–2074.
Journal cover image

Published In

J Allergy Clin Immunol

DOI

EISSN

1097-6825

Publication Date

June 2019

Volume

143

Issue

6

Start / End Page

2062 / 2074

Location

United States

Related Subject Headings

  • Interleukin-5 Receptor alpha Subunit
  • Infant, Newborn
  • Humans
  • Genome-Wide Association Study
  • Epigenome
  • Epigenesis, Genetic
  • ERG1 Potassium Channel
  • DNA Methylation
  • Cross-Sectional Studies
  • CpG Islands