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:
CreatorsEmailORCIDORCID Put Code
Sharma, V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michel, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gaertner, V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franke, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vogelberg, C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
von Berg, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bufe, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinzmann, A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laub, O.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rietschel, E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Simma, B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frischer, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Genuneit, J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeilinger, S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Illig, T.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schedel, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Potaczek, D. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kabesch, M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
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:
KeywordsLanguage
CLASS SWITCH RECOMBINATION; RI-ALPHA GENE; WIDE ASSOCIATION; ASTHMA; POLYMORPHISMS; PATHOGENESIS; VARIANTS; ALLERGY; LINKAGEMultiple languages
Allergy; ImmunologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/43295

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