Genomewide association study of peanut allergy reproduces association with amino acid polymorphisms in HLA-DRB1
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. Vukevic
- A. Motyer
- S. Leslie
- K.J. Allen
- M.A.R. Ferreira
Journal
- Clinical and Experimental Allergy
Citation
- Clin Exp Allergy 47 (2): 217-223
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 x 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 x 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.