Genomewide 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 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.

• Authors: D J Martino, S Ashley, J Koplin, J Ellis, R Saffery, S C Dharmage, L Gurrin, M C Matheson, B Kalb, I Marenholz, K Beyer, Y-A Lee, X Hong, X Wang, D Vukcevic, A Motyer, S Leslie, K J Allen, M A R Ferreira
• Journal: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology (Clin Exp Allergy) Vol. 47 Issue 2 Pg. 217-223 (Feb 2017) ISSN: 1365-2222 [Electronic] England
• PMID: 27883235 (Publication Type: Journal Article)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

• HLA-DRB1 Chains

Topics

• Alleles
• Amino Acid Substitution
• Genetic Predisposition to Disease
• Genome-Wide Association Study
• Genotype
• HLA-DRB1 Chains (chemistry, genetics, immunology)
• Humans
• Odds Ratio
• Peanut Hypersensitivity (genetics, immunology)
• Polymorphism, Genetic
• Polymorphism, Single Nucleotide