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

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.; Ferreira, M.A.R.

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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