@article{96baaa9a1cf6407f969ef3d0abafc41e,
title = "Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children",
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 × 10 -8) and rs9275596 (P=6.8 × 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 × 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.",
author = "Xiumei Hong and Ke Hao and Christine Ladd-Acosta and Hansen, {Kasper D.} and Tsai, {Hui Ju} and Xin Liu and Xin Xu and Thornton, {Timothy A.} and Deanna Caruso and Keet, {Corinne A.} and Yifei Sun and Guoying Wang and Wei Luo and Rajesh Kumar and Ramsay Fuleihan and Singh, {Anne Marie} and Kim, {Jennifer S.} and Story, {Rachel E.} and Gupta, {Ruchi S.} and Peisong Gao and Zhu Chen and Walker, {Sheila O.} and Bartell, {Tami R.} and Beaty, {Terri H.} and Fallin, {M. Daniele} and Robert Schleimer and Holt, {Patrick G.} and Nadeau, {Kari Christine} and Wood, {Robert A.} and Pongracic, {Jacqueline A.} and Weeks, {Daniel E.} and Xiaobin Wang",
note = "Funding Information: We gratefully acknowledge the individuals and families who participated in the Chicago Food Allergy Study. This research was supported in part by grants from the Bunning Family and their family foundations, Sacks Family Foundation Fund, Food Allergy Research and Education (FARE) and the National Institute of Allergy and Infectious Diseases (NIAID, PI: X.W., U01AI090727 from the Consortium of Food Allergy Research, R56AI080627 and R21AI088609). Dr Hui-Ju Tsai was supported by a grant MOST 103-2314-B-400-004-MY3. We also acknowledge Drs I-Shou Chang, Wen-Chang Wang and Mr Lan-Chao Wang for their assistance in GWAS data cleaning, and acknowledge Dr Jean-Philippe Fortin for his assistance in DNAm data cleaning. Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited. All rights reserved.",
year = "2015",
month = mar,
doi = "10.1038/ncomms7304",
language = "English (US)",
volume = "6",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}