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Clin Exp Allergy. 2017 Feb;47(2):217-223. doi: 10.1111/cea.12863. Epub 2017 Jan 11.

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

Author information

1
Department of Paediatrics, Murdoch Childrens Research Institute, The Royal Children's Hospital, The University of Melbourne, Melbourne, Vic., Australia.
2
Hudson Institute of Medical Research, Clayton, Vic., Australia.
3
School of Population and Global Health, The University of Melbourne, Melbourne, Vic., Australia.
4
Pediatric Pneumology and Immunology, Charité Universitätsmedizin Berlin, Berlin, Germany.
5
Clinic for Pediatric Allergy, Experimental and Clinical Research Center of MDC, Charité, Berlin, Germany.
6
Max-Delbrück-Center for Molecular Medicine (MDC), Berlin, Germany.
7
Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
8
Centre for Systems Genomics, Schools of Mathematics and Statistics and Biosciences, The University of Melbourne, Melbourne, Vic., Australia.
9
QIMR Berghofer Medical Research Institute, Brisbane, Qld, Australia.

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.

KEYWORDS:

GWAS ; food allergy; genetics; hypersensitivity; peanut allergy

PMID:
27883235
DOI:
10.1111/cea.12863
[Indexed for MEDLINE]

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