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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)217-223
Number of pages7
JournalClinical and Experimental Allergy
Volume47
Issue number2
DOIs
StatePublished - Feb 1 2017

Keywords

  • GWAS
  • food allergy
  • genetics
  • hypersensitivity
  • peanut allergy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    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. (2017). Genomewide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1. Clinical and Experimental Allergy, 47(2), 217-223. https://doi.org/10.1111/cea.12863