Genome-Wide Scan on Total Serum IgE Levels Identifies FCER1A as Novel Susceptibility Locus

• DOI: 10.1371/journal.pgen.1000166
• Publication Date: 2008-08-21T22:10:05Z
• Authors: Stephan Weidinger; Christian Gieger; Elke Rodriguez; Hansjörg Baurecht; Martin Mempel; Norman Klopp; Henning Gohlke; Stefan Wagenpfeil; Markus Ollert; Johannes Ring; Heidrun Behrendt; Joachim Heinrich; Natalija Novak; Thomas Bieber; Ursula Krämer; Dietrich Berdel; Andrea von Berg; Carl Peter Bauer; Olf Herbarth; Sibylle Koletzko; Holger Prokisch; Divya Mehta; Thomas Meitinger; Martin Depner; Erika von Mutius; Liming Liang; Miriam Moffatt; William Cookson; Michael Kabesch; H.-Erich Wichmann; Thomas Illig
• Keywords: Genome-wide Association Study; Genetic Association

High levels of serum IgE are considered markers parasite and helminth exposure. In addition, they associated with allergic disorders, play a key role in anti-tumoral defence, crucial mediators autoimmune diseases. Total is strongly heritable trait. genome-wide association study (GWAS), we tested 353,569 SNPs for 1,530 individuals from the population-based KORA S3/F3 study. Replication was performed four independent samples (total n = 9,769 individuals). Functional variants gene encoding alpha chain high affinity receptor (FCER1A) on chromosome 1q23 (rs2251746 rs2427837) were total all cohorts P values 1.85 x 10(-20) 7.08 10(-19) combined analysis, post-hoc analysis showed additional associations sensitization (P 7.78 10(-4) 1.95 10(-3)). The "top" SNP significantly influenced cell surface expression FCER1A basophils, profiles indicated an interesting novel regulatory mechanism via GATA-2. Polymorphisms within RAD50 5q31 consistently 6.28 10(-7)-4.46 10(-8)) increased risk atopic eczema asthma. Furthermore, STAT6 confirmed as susceptibility locus modulating levels. this first GWAS identified replicated new at which common genetic variation influences might represent factors cytokine cluster 5q31, emphasizing need further investigations intriguing region. Our data furthermore confirm