Cited by 223Epigenetics and DNA MethylationAsthma and respiratory diseasesAllergic Rhinitis and Sensitization

An epigenome-wide association study of total serum immunoglobulin E concentration

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Liang, Liming, Willis-Owen, Saffron A. G., Laprise, Catherine, Wong, Kenny C. C., Davies, Gwyneth A., Hudson, Thomas J., Binia, Aristea, Hopkin, Julian M. +10 more·2015·Nature

Abstract

Immunoglobulin E (IgE) is a central mediator of allergic (atopic) inflammation. Therapies directed against IgE can alleviate hay fever and allergic asthma. Genetic association studies have not yet identified novel therapeutic targets or pathways underlying IgE regulation. We therefore surveyed epigenetic associations between serum IgE concentrations and methylation at loci concentrated in CpG islands genome wide in 95 nuclear pedigrees, using DNA from peripheral blood leukocytes. We validated positive results in additional families and in subjects from the general population. Here we show replicated associations--with a meta-analysis false discovery rate less than 10(-4)--between IgE and low methylation at 36 loci. Genes annotated to these loci encode known eosinophil products, and also implicate phospholipid inflammatory mediators, specific transcription factors and mitochondrial proteins. We confirmed that methylation at these loci differed significantly in isolated eosinophils from subjects with and without asthma and high IgE levels. The top three loci accounted for 13% of IgE variation in the primary subject panel, explaining the tenfold higher variance found compared with that derived from large single-nucleotide polymorphism genome-wide association studies. This study identifies novel therapeutic targets and biomarkers for patient stratification for allergic diseases.

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  • Several studies have convincingly linked methylation profiles to allergic rhinitis and IgE-related outcomes, but large-scale studies have yet to be completed.

    “Several studies have convincingly linked methylation profiles to AR507-509 and IgE-related outcomes,510,511 but large-scale studies have yet to be completed.”

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Authors
Liang, L., Willis-Owen, S. A. G., Laprise, C., Wong, K. C. C., Davies, G. A., Hudson, T. J., Binia, A., Hopkin, J. M., Yang, I. V., Grundberg, E., Busche, S., Hudson, M., Rönnblom, L., Pastinen, T. M., Schwartz, D. A., Lathrop, G. M., Moffatt, M. F., & Cookson, W. O. C. M.
Affiliations
  • Harvard University (US)
  • Université du Québec à Chicoutimi (CA)
  • Imperial College London (GB)
  • Swansea University (GB)
  • Ontario Institute for Cancer Research (CA)
  • National Jewish Health (US)
  • McGill University and Génome Québec Innovation Centre (CA)
  • Jewish General Hospital (CA)
  • Uppsala University (SE)
  • McGill University Health Centre (CA)
Corresponding author
Cookson, William O. C. M.
Venue
Nature
Published
2015-02-18
Volume
520
Issue
7549
Pages
670-674
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2154532141
Cited by
213
References
36
Citations by year
2026: 4 · 2025: 6 · 2024: 4 · 2023: 11 · 2022: 13 · 2021: 19 · 2020: 25 · 2019: 20 · 2018: 29 · 2017: 28 · 2016: 35 · 2015: 17 · 2014: 1
FWCI
3.52
Type
journal article
Language
en
Open access
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Spiral (Imperial College London) (submittedVersion)
Funders
  • Wellcome Trust (WT077959, 096964, 097117, WT096964, 077959, 096964/Z/11/Z)
  • National Institute for Health and Care Research (NF-SI-0512-10126)
  • National Institutes of Health (5r01hl101251-05)
  • Medical Research Council (MR/K006525/1)
  • National Heart, Lung, and Blood Institute (R01-HL101251, R01 HL101251-01)
  • National Institute of Environmental Health Sciences (P01 ES18181, P01ES018181)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
  • Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
Keywords
serum IgE, DNA methylation, CpG islands, epigenome-wide association study, allergic diseases, asthma, eosinophils, therapeutic target, biomarkers, patient stratification, peripheral blood leukocytes
MeSH terms
Adolescent, Adult, Asthma, Child, Eosinophils, Female, Humans, Immunoglobulin E, Male, Middle Aged, Pedigree, Transcription Factors, Genome, Human, Inflammation Mediators, CpG Islands, DNA Methylation, Polymorphism, Single Nucleotide, Mitochondrial Proteins, Epigenesis, Genetic, Young Adult, Genetic Association Studies

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