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

Hong, X.; Hao, K.; Ladd-Acosta, C.; Hansen, K. D.; Tsai, H. J.; Liu, X.; Xu, X.; Thornton, T. A.; Caruso, D.; Keet, C. A.; Sun, Y.; Wang, G.; Luo, W.; Kumar, R.; Fuleihan, R.; Singh, A. M.; Kim, J. S.; Story, R. E.; Gupta, R. S.; Gao, P.; Chen, Z.; Walker, S. O.; Bartell, T. R.; Beaty, T. H.; Fallin, M. D.; Schleimer, R.; Holt, P. G.; Nadeau, K. C.; Wood, R. A.; Pongracic, J. A.; Weeks, D. E.; Wang, X.

Nat Commun. 2015 Feb 25; 6:6304


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.

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