@article{1281de9e64184efe9ced877dc2036855,
title = "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.",
keywords = "GWAS, food allergy, genetics, hypersensitivity, peanut allergy",
author = "Martino, {D. J.} and S. Ashley and J. Koplin and J. Ellis and R. Saffery and Dharmage, {S. C.} and L. Gurrin and Matheson, {M. C.} and B. Kalb and I. Marenholz and K. Beyer and Lee, {Y. A.} and X. Hong and X. Wang and D. Vukcevic and A. Motyer and S. Leslie and Allen, {K. J.} and Ferreira, {M. A.R.}",
note = "Funding Information: The genomewide association in this study was funded by the US Department of Defense (grant # W81XWH-10-1-0487). The HealthNuts cohort is funded by the Australian National Health and Medical Research Council. This work was supported by the Australian National Health and Medical Research Council (NHMRC), Career Development Fellowship ID 1053756 (SL) Australian Research Council Future Fellowship ID FT120100253 (JE), Early Career Fellowships 1072752, 1054592 (DM, JE) and the Victorian Life Sciences Computation Initiative (VLSCI) grant number VR0240 on its Peak Computing Facility at the University of Melbourne, an initiative of the Victorian Government, Australia (SL). Research at the Murdoch Childrens Research Institute was supported by the Victorian Government{\textquoteright}s Operational Infrastructure Support Program. SL is a partner in Peptide Groove LLP. The UFA study was supported by a Clinical Exchange Program fellowship of the Experimental and Clinical Research Center of Max-Delbr{\"u}ck-Center and Charit{\'e} Medical School. We thank Markus M Noethen (Institute of Human Genetics, University of Bonn, Germany) and Sven Cichon (Division of Medical Genetics, University Hospital Basel and Department of Biomedicine, University of Basel) for providing genotype data of the Heinz Nixdorf RECALL (HNR) study. Publisher Copyright: {\textcopyright} 2016 John Wiley & Sons Ltd",
year = "2017",
month = feb,
day = "1",
doi = "10.1111/cea.12863",
language = "English (US)",
volume = "47",
pages = "217--223",
journal = "Clinical Allergy",
issn = "0954-7894",
publisher = "Wiley-Blackwell",
number = "2",
}