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Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children

TitleGenome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children
Publication TypeJournal Article
Year of Publication2015
AuthorsHong, X, Hao, K, Ladd-Acosta, C, Hansen, KD, Tsai, HJ, Liu, X, Xu, X, Thornton, TA, Caruso, D, Keet, CA, Sun, Y, Wang, G, Luo, W, Kumar, R, Fuleihan, R, Singh, AM, Kim, JS, Story, RE, Gupta, RS, Gao, P, Chen, Z, Walker, SO, Bartell, TR, Beaty, TH, Fallin, MD, Schleimer, R, Holt, PG, Nadeau, KC, Wood, RA, Pongracic, JA, Weeks, DE, Wang, X
JournalNat Commun
Volume6
Pagination6304
ISBN Number2041-1723 (Electronic)2041-1723 (Linking)
Accession Number25710614
Abstract

Food allergy (FA) affects 2%-10% of US children and is a growing clinical and public health problem. Here we conduct the first genome-wide association study of well-defined FA, including specific subtypes (peanut, milk and egg) in 2,759 US participants (1,315 children and 1,444 parents) from the Chicago Food Allergy Study, and identify peanut allergy (PA)-specific loci in the HLA-DR and -DQ gene region at 6p21.32, tagged by rs7192 (P=5.5 x 10(-8)) and rs9275596 (P=6.8 x 10(-10)), in 2,197 participants of European ancestry. We replicate these associations in an independent sample of European ancestry. These associations are further supported by meta-analyses across the discovery and replication samples. Both single-nucleotide polymorphisms (SNPs) are associated with differential DNA methylation levels at multiple CpG sites (P<5 x 10(-8)), and differential DNA methylation of the HLA-DQB1 and HLA-DRB1 genes partially mediate the identified SNP-PA associations. This study suggests that the HLA-DR and -DQ gene region probably poses significant genetic risk for PA.

PMCID

PMC4340086