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

Autor: Liang L; Departments of Epidemiology and Biostatistics, Harvard School of Public Health, Boston, MA 02115., Willis-Owen SAG; National Heart and Lung Institute, Imperial College, London SW3 6LY, UK., Laprise C; Université du Québec à Chicoutimi, Saguenay, Québec, Canada., Wong KCC; National Heart and Lung Institute, Imperial College, London SW3 6LY, UK., Davies GA; Institute of Life Science, College of Medicine, Swansea University, SA2 8PP, UK., Hudson TJ; Ontario Institute for Cancer Research, Toronto, Ontario Canada, M5G 0A3.; Departments of Medical Biophysics and Molecular Genetics, University of Toronto, Canada ON M5S 1A1., Binia A; National Heart and Lung Institute, Imperial College, London SW3 6LY, UK., Hopkin JM; Institute of Life Science, College of Medicine, Swansea University, SA2 8PP, UK., Yang IV; University of Colorado School of Medicine and National Jewish Health, Denver, CO 80206., Grundberg E; Department of Human Genetics, McGill University and Génome Québec Innovation Centre, Montréal, Canada., Busche S; Department of Human Genetics, McGill University and Génome Québec Innovation Centre, Montréal, Canada., Hudson M; Jewish General Hospital and Lady Davis Research Institute, Montréal, Canada H3T 1E2., Rönnblom L; Department of Medical Sciences, SciLifeLab, Uppsala University, Uppsala, Sweden., Pastinen TM; Department of Human Genetics, McGill University and Génome Québec Innovation Centre, Montréal, Canada.; Department of Medical Genetics, McGill University Health Centre, Montréal, Canada., Schwartz DA; University of Colorado School of Medicine and National Jewish Health, Denver, CO 80206., Lathrop GM; Department of Human Genetics, McGill University and Génome Québec Innovation Centre, Montréal, Canada., Moffatt MF; National Heart and Lung Institute, Imperial College, London SW3 6LY, UK., Cookson WOCM; National Heart and Lung Institute, Imperial College, London SW3 6LY, UK.
Jazyk: angličtina
Zdroj: Nature [Nature] 2015 Apr 30; Vol. 520 (7549), pp. 670-674. Date of Electronic Publication: 2015 Feb 18.
DOI: 10.1038/nature14125
Abstrakt: 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.
Databáze: MEDLINE