RT Journal Article SR Electronic T1 Fine-mapping of IgE associated loci 1q23, 5q31 and 12q13 JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP P4215 VO 44 IS Suppl 58 A1 Vishwas Sharma A1 Sven Michel A1 Vincent Gaertner A1 Andre Franke A1 Christian Vogelberg A1 Andrea von Berg A1 Albrecht Bufe A1 Andrea Heinzmann A1 Otto Laub A1 Ernst Rietschel A1 Burkhard Simma A1 Thomas Frischer A1 Jon Genuneit A1 Sonja Zeilinger A1 Thomas Illig A1 Michaela Schedel A1 Daniel Potaczek A1 Michael Kabesch YR 2014 UL http://erj.ersjournals.com/content/44/Suppl_58/P4215.abstract AB 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.