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

Abstract

Background

Genetic variants for IgE-mediated peanut allergy are yet to be fully characterized and to date only one genome-wide 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 polymorphism (SNPs), 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 ≤ 5x10^-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 = 2x10^-4). Our study therefore reproduced previous findings for the association between peanut allergy and HLA-DRB1 in this Australian population.

Conclusions & Clinical Relevance

Genetic determinants for challenge proven peanut allergy include alleles at the HLA-DRB1 locus.

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