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Meta-Analysis
. 2012 Mar;129(3):840-845.e21.
doi: 10.1016/j.jaci.2011.09.029. Epub 2011 Nov 9.

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

Mark Granada  1 , Jemma B Wilk, Marina Tuzova, David P Strachan, Stephan Weidinger, Eva Albrecht, Christian Gieger, Joachim Heinrich, Blanca E Himes, Gary M Hunninghake, Juan C Celedón, Scott T Weiss, William W Cruikshank, Lindsay A Farrer, David M Center, George T O'Connor
Affiliations
Meta-Analysis

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

Mark Granada et al. J Allergy Clin Immunol. 2012 Mar.

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: 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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Figure 1
Figure 1
Genome wide association results for imputed SNPs and plasma total IgE concentration in the Framingham Heart Study. Coordinates on the X-axis represent chromosomes. Negative logarithm p-values are shown on the y-axis
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