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An epigenome-wide association study of total serum immunoglobulin E concentration
Open accessAbstract
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 AR507-509 and IgE-related outcomes,510,511 but large-scale studies have yet to be completed.”
From International Consensus Statement on Allergy and Rhinology: Allergic Rhinitis (2018) · cites this paper as [510]
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Metadata
- 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.
- ORCID
- Venue
- Nature
- Published
- 2015-02-18
- Volume
- 520
- Issue
- 7549
- Pages
- 670-674
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4416961
- 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
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- 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 › Pulmonary and Respiratory Medicine › 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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