Universität zu Köln

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., Genuneit, J., Zeilinger, S., Illig, T., Schedel, M., Potaczek, D. P. and Kabesch, M. (2014). Fine-mapping of IgE-associated loci 1q23, 5q31, and 12q13 using 1000 Genomes Project data. Allergy, 69 (8). S. 1077 - 1085. HOBOKEN: WILEY. ISSN 1398-9995

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Sharma, V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Michel, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gaertner, V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Franke, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Vogelberg, C. UNSPECIFIED UNSPECIFIED UNSPECIFIED von Berg, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bufe, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Heinzmann, A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Laub, O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rietschel, E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Simma, B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Frischer, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Genuneit, J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Zeilinger, S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Illig, T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Schedel, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Potaczek, D. P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kabesch, M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-432955
DOI:	10.1111/all.12431
Journal or Publication Title:	Allergy
Volume:	69
Number:	8
Page Range:	S. 1077 - 1085
Date:	2014
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1398-9995
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CLASS SWITCH RECOMBINATION; RI-ALPHA GENE; WIDE ASSOCIATION; ASTHMA; POLYMORPHISMS; PATHOGENESIS; VARIANTS; ALLERGY; LINKAGE Multiple languages Allergy; Immunology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43295