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; 6:6304


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.


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