Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus

Weidinger, Stephan, Gieger, Christian, Rodriguez, Elke, Baurecht, Hansjoerg, Mempel, Martin, Klopp, Norman, Gohlke, Henning, Wagenpfeil, Stefan, Ollert, Markus, Ring, Johannes, Behrendt, Heidrun, Heinrich, Joachim, Novak, Natalija, Bieber, Thomas, Kraemer, Ursula, Berdel, Dietrich, von Berg, Andrea, Bauer, Carl Peter, Herbarth, Olf, Koletzko, Sibylle, Prokisch, Holger, Mehta, Divya, Meitinger, Thomas, Depner, Martin, von Mutius, Erika, Liang, Liming, Moffatt, Miriam, Cookson, William, Kabesch, Michael, Wichmann, H. -Erich and Illig, Thomas (2008) Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus. PLoS Genetics, 4 8: e1000166.1-e1000166.9. doi:10.1371/journal.pgen.1000166

Author Weidinger, Stephan
Gieger, Christian
Rodriguez, Elke
Baurecht, Hansjoerg
Mempel, Martin
Klopp, Norman
Gohlke, Henning
Wagenpfeil, Stefan
Ollert, Markus
Ring, Johannes
Behrendt, Heidrun
Heinrich, Joachim
Novak, Natalija
Bieber, Thomas
Kraemer, Ursula
Berdel, Dietrich
von Berg, Andrea
Bauer, Carl Peter
Herbarth, Olf
Koletzko, Sibylle
Prokisch, Holger
Mehta, Divya
Meitinger, Thomas
Depner, Martin
von Mutius, Erika
Liang, Liming
Moffatt, Miriam
Cookson, William
Kabesch, Michael
Wichmann, H. -Erich
Illig, Thomas
Title Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus
Journal name PLoS Genetics   Check publisher's open access policy
ISSN 1553-7390
Publication date 2008
Year available 2008
Sub-type Article (original research)
DOI 10.1371/journal.pgen.1000166
Open Access Status DOI
Volume 4
Issue 8
Start page e1000166.1
End page e1000166.9
Total pages 9
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2008
Language eng
Abstract High levels of serum IgE are considered markers of parasite and helminth exposure. In addition, they are associated with allergic disorders, play a key role in anti-tumoral defence, and are crucial mediators of autoimmune diseases. Total IgE is a strongly heritable trait. In a genome-wide association study (GWAS), we tested 353,569 SNPs for association with serum IgE levels in 1,530 individuals from the population-based KORA S3/F3 study. Replication was performed in four independent population-based study samples (total n = 9,769 individuals). Functional variants in the gene encoding the alpha chain of the high affinity receptor for IgE (FCER1A) on chromosome 1q23 (rs2251746 and rs2427837) were strongly associated with total IgE levels in all cohorts with P values of 1.85 × 10-20 and 7.08 × 10-19 in a combined analysis, and in a post-hoc analysis showed additional associations with allergic sensitization (P = 7.78 × 10-4 and P = 1.95 × 10-3). The "top" SNP significantly influenced the cell surface expression of FCER1A on basophils, and genome-wide expression profiles indicated an interesting novel regulatory mechanism of FCER1A expression via GATA-2. Polymorphisms within the RAD50 gene on chromosome 5q31 were consistently associated with IgE levels (P values 6.28 × 10 -7-4.46 × 10-8) and increased the risk for atopic eczema and asthma. Furthermore, STAT6 was confirmed as susceptibility locus modulating IgE levels. In this first GWAS on total IgE FCER1A was identified and replicated as new susceptibility locus at which common genetic variation influences serum IgE levels. In addition, variants within the RAD50 gene might represent additional factors within cytokine gene cluster on chromosome 5q31, emphasizing the need for further investigations in this intriguing region. Our data furthermore confirm association of STAT6 variation with serum IgE levels.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 150 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 24 Oct 2014, 17:12:48 EST by Sylvie Pichelin on behalf of Queensland Brain Institute