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

• Published in: Clinical and experimental allergy Vol. 47; no. 2; pp. 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: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-02-2017
• 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; peanut allergy; GWAS; genetics; hypersensitivity; food allergy
• ISSN: 0954-7894; 1365-2222
• DOI: 10.1111/cea.12863

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.