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

Abstract

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 To ascertain the genetic risk factors which lead to IgE dysregulation. Methods A genome wide association study (GWAS) was performed in 6,819 participants from the Framingham Heart Study (FHS). Seventy of the top SNPs were selected based on p-values and linkage disequilibrium among neighboring SNPs and evaluated in a meta-analysis with five independent populations from the KORA, B58C, and CAMP cohorts. Results Thirteen SNPs located in the region of three genes, FCER1A, STAT6, and IL-13, were found to have genome-wide significance in the FHS GWAS. The most significant SNPs from the three regions were rs2251746 (FCER1A, p-value 2.11×10-12), rs1059513 (STAT6, p-value 2.87×10-08), and rs1295686 (IL-13, p-value 3.55×10-08). Four additional gene regions - HLA-G, HLA-DQA2, HLA-A, and DARC - reached genome-wide statistical significance in meta-analysis combining 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 has identified genetic loci in HLA genes that may have a role in the pathogenesis of IgE dysregulation and atopy. It also confirmed the association of known susceptibility loci, FCER1A, STAT6, and IL-13, for the dysregulation of total IgE.

Identification of IL13 C1923T as a Single Nucleotide Polymorphism for Asthma in Children from Mauritius

“…25 However, no research has previously been done to investigate the genes and SNPs predisposing to asthma in the Mauritian population. The rs1295686 has been associated with the dysregulation of total IgE, 26 which is a major factor in the development of asthma, 27 but its role in the pathogenesis of asthma for the pediatric population has not been fully understood.…”

Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals

“…[34][35][36][37] Other variants in FCER1A, a subunit of the allergy response IgE receptor and basophil differentiation factor, have previously been associated with IgE levels and monocyte counts. 38,39 Increased platelet activation has been postulated to contribute to or be a consequence of allergic and inflammatory responses. 40 Our association of rare deleterious variation in FCER1A to reduced PLT provides a further link between platelet biology and allergy response.…”

Discovering susceptibility genes for allergic rhinitis and allergy using a genome-wide association study strategy

“…The first GWAS of IgE serum levels in asthma patients identified associated variants mapping to FCER1A (alpha chain of the high-affinity receptor for IgE) at 1q23, STAT6 at 12q13 and IL-13-RAD50 at 5q31 region [45]. Subsequently, two GWASs confirmed the associations of these loci with serum IgE levels [10,46]. More recently, one study [47] has indicated that variants in FCER1A were associated with allergic diseases including asthma, allergic rhinitis and allergic sensitization defined by skin prick test (SPT).…”