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

Summary 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 com...

Full description

Saved in:
Bibliographic Details
Published in:Clinical and experimental allergy 2017-02, Vol.47 (2), p.217-223
Main Authors: 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., Vukcevic, D., Motyer, A., Leslie, S., Allen, K. J., Ferreira, M. A. R.
Format: Article
Language:English
Subjects:
Alleles
Amino Acid Substitution
Arachis hypogaea
Food allergies
food allergy
Genetic Predisposition to Disease
genetics
Genome-Wide Association Study
Genotype
GWAS
HLA-DRB1 Chains - chemistry
HLA-DRB1 Chains - genetics
HLA-DRB1 Chains - immunology
Humans
hypersensitivity
Odds Ratio
peanut allergy
Peanut Hypersensitivity - genetics
Peanut Hypersensitivity - immunology
Peanuts
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary 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 × 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 × 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.
ISSN:0954-7894
1365-2222
DOI:10.1111/cea.12863