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Fine-mapping of IgE-associated loci 1q23, 5q31, and 12q13 using 1000 Genomes Project data.
Allergy 2014; 69(8):1077-84A

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.

Authors+Show Affiliations

Department of Pediatric Pneumology, Allergy and Neonatology, Hannover Medical School, Hannover, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24930997

Citation

Sharma, V, et al. "Fine-mapping of IgE-associated Loci 1q23, 5q31, and 12q13 Using 1000 Genomes Project Data." Allergy, vol. 69, no. 8, 2014, pp. 1077-84.
Sharma V, Michel S, Gaertner V, et al. Fine-mapping of IgE-associated loci 1q23, 5q31, and 12q13 using 1000 Genomes Project data. Allergy. 2014;69(8):1077-84.
Sharma, V., Michel, S., Gaertner, V., Franke, A., Vogelberg, C., von Berg, A., ... Kabesch, M. (2014). Fine-mapping of IgE-associated loci 1q23, 5q31, and 12q13 using 1000 Genomes Project data. Allergy, 69(8), pp. 1077-84. doi:10.1111/all.12431.
Sharma V, et al. Fine-mapping of IgE-associated Loci 1q23, 5q31, and 12q13 Using 1000 Genomes Project Data. Allergy. 2014;69(8):1077-84. PubMed PMID: 24930997.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fine-mapping of IgE-associated loci 1q23, 5q31, and 12q13 using 1000 Genomes Project data. AU - Sharma,V, AU - Michel,S, AU - Gaertner,V, AU - Franke,A, AU - Vogelberg,C, AU - von Berg,A, AU - Bufe,A, AU - Heinzmann,A, AU - Laub,O, AU - Rietschel,E, AU - Simma,B, AU - Frischer,T, AU - Genuneit,J, AU - Zeilinger,S, AU - Illig,T, AU - Schedel,M, AU - Potaczek,D P, AU - Kabesch,M, Y1 - 2014/06/14/ PY - 2014/04/17/accepted PY - 2014/6/17/entrez PY - 2014/6/17/pubmed PY - 2015/6/25/medline KW - asthma KW - atopy KW - fine-mapping KW - genetic polymorphisms KW - immunoglobulin E SP - 1077 EP - 84 JF - Allergy JO - Allergy VL - 69 IS - 8 N2 - 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. SN - 1398-9995 UR - https://www.unboundmedicine.com/medline/citation/24930997/Fine_mapping_of_IgE_associated_loci_1q23_5q31_and_12q13_using_1000_Genomes_Project_data_ L2 - https://doi.org/10.1111/all.12431 DB - PRIME DP - Unbound Medicine ER -