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Genomewide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1

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Item Type:Article
Title:Genomewide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1
Creators Name:Martino, D.J., Ashley, S., Koplin, J., Ellis, J., Saffery, R., Dharmage, S.C., Gurrin, L., Matheson, M.C., Kalb, B., Marenholz, I., Beyer, K., Lee, Y.A., Hong, X., Wang, X., Vukevic, D., Motyer, A., Leslie, S., Allen, K.J. and Ferreira, M.A.R.
Abstract:BACKGROUND: Genetic variants for IgE-mediated peanut allergy are yet to be fully characterized and to date only one genomewide association study (GWAS) has been published. OBJECTIVE: To identify genetic variants associated with challenge-proven peanut allergy. METHODS: We carried out a GWAS comparing 73 infants with challenge-proven IgE-mediated peanut allergy against 148 non-allergic infants (all ~ 1 year old). We tested a total of 3.8 million single nucleotide polymorphisms, as well as imputed HLA alleles and amino acids. Replication was assessed by de novo genotyping in a panel of additional 117 cases and 380 controls, and in silico testing in two independent GWAS cohorts. RESULTS: We identified 21 independent associations at P </= 5 x 10-5 but were unable to replicate these. The most significant HLA association was the previously reported amino acid variant located at position 71, within the peptide-binding groove of HLA-DRB1 (P = 2 x 10-4 ). Our study therefore reproduced previous findings for the association between peanut allergy and HLA-DRB1 in this Australian population. CONCLUSIONS AND CLINICAL RELEVANCE: Genetic determinants for challenge-proven peanut allergy include alleles at the HLA-DRB1 locus.
Keywords:Food Allergy, Genetics, GWAS, Hypersensitivity, Peanut Allergy
Source:Clinical and Experimental Allergy
ISSN:0954-7894
Publisher:Wiley-Blackwell
Volume:47
Number:2
Page Range:217-223
Date:February 2017
Additional Information:Copyright © 2016 John Wiley & Sons Ltd
Official Publication:https://doi.org/10.1111/cea.12863
PubMed:View item in PubMed

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