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Granada, M.* ; Wilk, J.B.* ; Tuzova, M.* ; Strachan, D.P.* ; Weidinger, S.* ; Albrecht, E. ; Gieger, C. ; Heinrich, J. ; Himes, B.E.* ; Hunninghake, G.M.* ; Celedón, J.C.* ; Weiss, S.T.* ; Cruikshank, W.W.* ; Farrer, L.A.* ; Center, D.M.* ; O'Connor, G.T.*

A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study.

J. Allergy Clin. Immunol. 129, 840-845 (2012)
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BACKGROUND: Atopy and plasma IgE concentration are genetically complex traits, and the specific genetic risk factors that lead to IgE dysregulation and clinical atopy are an area of active investigation. OBJECTIVE: We sought to ascertain the genetic risk factors that lead to IgE dysregulation. METHODS: A genome-wide association study (GWAS) was performed in 6819 participants from the Framingham Heart Study (FHS). Seventy of the top single nucleotide polymorphisms (SNPs) were selected based on P values and linkage disequilibrium among neighboring SNPs and evaluated in a meta-analysis with 5 independent populations from the Cooperative Health Research in the Region of Augsburg cohort, the British 1958 Birth Cohort, and the Childhood Asthma Management Program cohort. RESULTS: Thirteen SNPs located in the region of 3 genes, FCER1A, signal transducer and activator of transcription 6 (STAT6), and IL13, were found to have genome-wide significance in the FHS cohort GWAS. The most significant SNPs from the 3 regions were rs2251746 (FCER1A, P = 2.11 × 10(-12)), rs1059513 (STAT6, P = 2.87 × 10(-8)), and rs1295686 (IL13, P = 3.55 × 10(-8)). Four additional gene regions, HLA-G, HLA-DQA2, HLA-A, and Duffy blood group, chemokine receptor (DARC), reached genome-wide statistical significance in a meta-analysis combining the FHS and replication cohorts, although the DARC association did not appear independent of SNPs in the nearby FCER1A gene. CONCLUSION: This GWAS of the FHS cohort has identified genetic loci in HLA genes that might have a role in the pathogenesis of IgE dysregulation and atopy. It also confirmed the association of the known susceptibility loci FCER1A, STAT6, and IL13 for the dysregulation of total IgE.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Total IgE; atopy; asthma; genome-wide association study; IMMUNOGLOBULIN-E; ALLERGIC DISEASES; CHILDHOOD ASTHMA; HLA ANTIGENS; GENE; POPULATION; LINKAGE; STAT6; RISK; SUSCEPTIBILITY
Sprache
Veröffentlichungsjahr 2012
HGF-Berichtsjahr 2012
ISSN (print) / ISBN 0091-6749
e-ISSN 1097-6825
Zeitschrift The journal of allergy and clinical immunology
Quellenangaben Band: 129, Heft: 3, Seiten: 840-845 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort Amsterdam [u.a.]
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
POF Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30503 - Chronic Diseases of the Lung and Allergies
Forschungsfeld(er) Genetics and Epidemiology
PSP-Element(e) G-504100-001
G-503900-001
PubMed ID 22075330
DOI 10.1016/j.jaci.2011.09.029
WOS ID 000301189300033
Scopus ID 84857800654
Erfassungsdatum 2012-06-04
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