TY - JOUR T1 - Fine-mapping of IgE associated loci 1q23, 5q31 and 12q13 JF - European Respiratory Journal JO - Eur Respir J VL - 44 IS - Suppl 58 SP - P4215 AU - Vishwas Sharma AU - Sven Michel AU - Vincent Gaertner AU - Andre Franke AU - Christian Vogelberg AU - Andrea von Berg AU - Albrecht Bufe AU - Andrea Heinzmann AU - Otto Laub AU - Ernst Rietschel AU - Burkhard Simma AU - Thomas Frischer AU - Jon Genuneit AU - Sonja Zeilinger AU - Thomas Illig AU - Michaela Schedel AU - Daniel Potaczek AU - Michael Kabesch Y1 - 2014/09/01 UR - http://erj.ersjournals.com/content/44/Suppl_58/P4215.abstract N2 - Background: Three loci influencing total serum IgE levels 1q23 (FCER1A), 5q31 (RAD50-IL13 and IL4) and 12q13 (STAT6) were repeatedly identified by genome-wide association studies (GWAS). In order to determine causal variants which may have been missed by the GWAS, we performed fine-mapping and subsequent re-genotyping of the three loci taking also 1000 Genomes Project datasets into account.Methods: Selection criteria for polymorphisms to be re-genotyped (MALDI-TOF-MS of 40 polymorphisms) in at least 1,303 German children (651 asthmatics) were based on linkage disequilibrium and putative functional relevance. Overall the effect of 64 polymorphisms (24 polymorphisms were available due to previous array genotyping) on total serum IgE, IgE percentiles and atopic diseases were assessed. Gene by gene interaction was analyzed using a risk score model. Additionally, in silico studies on functional effects of putative causal variants from these three loci were performed.Results: We could confirm and extend previous GWAS findings. Interestingly different association patterns between the three loci were identified. While for 1q23 and 5q31 the majority of associations were found with mild to moderately elevated IgE levels, the SNPs of the 12q13 locus were associated with strongly elevated IgE levels. Gene by gene interaction analyses suggested an up to 4-fold increased risk for elevated IgE if mutations in all three loci are present.Conclusion: In addition to the confirmation of previous results, novel associations of SNPs in 1q23, 5q31 and 12q13 with different levels of serum IgE and their concomitant contribution to IgE regulation were identified. ER -