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A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study.
J. Allergy Clin. Immunol. 129, 840-845 (2012)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Total IgE; atopy; asthma; genome-wide association study; IMMUNOGLOBULIN-E; ALLERGIC DISEASES; CHILDHOOD ASTHMA; HLA ANTIGENS; GENE; POPULATION; LINKAGE; STAT6; RISK; SUSCEPTIBILITY
ISSN (print) / ISBN
0091-6749
e-ISSN
1097-6825
Quellenangaben
Volume: 129,
Issue: 3,
Pages: 840-845
Publisher
Elsevier
Publishing Place
Amsterdam [u.a.]
Non-patent literature
Publications
Reviewing status
Peer reviewed