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Sharma, V.* ; Michel, S.* ; Gaertner, V.* ; Franke, A.* ; Vogelberg, C.* ; von Berg, A.* ; Bufe, A.* ; Heinzmann, A.* ; Laub, O.* ; Rietschel, E.* ; Simma, B.* ; Frischer, T.H.* ; Genuneit, J.* ; Zeilinger, S. ; Illig, T. ; Schedel, M.* ; Potaczek, D.P.* ; Kabesch, M.*

Fine-mapping of IgE-associated loci 1q23, 5q31, and 12q13 using 1000 Genomes Project data.

Allergy 69, 1077-1084 (2014)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
Background: Genome-wide association studies (GWAS) repeatedly identified 1q23 (FCER1A), 5q31 (RAD50-IL13 and IL4), and 12q13 (STAT6) as major susceptibility loci influencing the regulation of total serum IgE levels. As GWAS may be insufficient to capture causal variants, we performed fine-mapping and re-genotyping of the three loci using 1000 Genomes Project datasets. Methods: Linkage disequilibrium tagging polymorphisms and polymorphisms of putative functional relevance were genotyped by chip technology (24 polymorphisms) or MALDI-TOF-MS (40 polymorphisms) in at least 1303 German children (651 asthmatics). The effect of polymorphisms on total serum IgE, IgE percentiles, and atopic diseases was assessed, and a risk score model was applied for gene-by-gene interaction analyses. Functional effects of putative causal variants from these three loci were studied in silico. Results: Associations from GWAS were confirmed and extended. For 1q23 and 5q31, the majority of associations were found with mild to moderately elevated IgE levels, while in the 12q13 locus, single-nucleotide polymorphisms (SNPs) were associated with strongly elevated IgE levels. Gene-by-gene interaction analyses suggested that the presence of mutations in all three loci increases the risk for elevated IgE up to fourfold. Conclusion: This fine-mapping study confirmed previous associations and identified novel associations of SNPs in 1q23, 5q31, and 12q13 with different levels of serum IgE and their concomitant contribution to IgE regulation.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Asthma ; Atopy ; Fine-mapping ; Genetic Polymorphisms ; Immunoglobulin E; Class-switch Recombination; Ri-alpha Gene; Wide Association; Childhood Asthma; Polymorphisms; Pathogenesis; Populations; Variants; Children; Allergy
ISSN (print) / ISBN 0105-4538
e-ISSN 1398-9995
Journal Allergy
Quellenangaben Volume: 69, Issue: 8, Pages: 1077-1084 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)