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

Xiumei Hong; Ke Hao; Christine Ladd-Acosta; Kasper D. Hansen; Hui Ju Tsai; Xin Liu; Xin Xu; Timothy A. Thornton; Deanna Caruso; Corinne A. Keet; Yifei Sun; Guoying Wang; Wei Luo; Rajesh Kumar; Ramsay Fuleihan; Anne Marie Singh; Jennifer S. Kim; Rachel E. Story; Ruchi S. Gupta; Peisong Gao; Zhu Chen; Sheila O. Walker; Tami R. Bartell; Terri H. Beaty; M. Daniele Fallin; Robert Schleimer; Patrick G. Holt; Kari Christine Nadeau; Robert A. Wood; Jacqueline A. Pongracic; Daniel E. Weeks; Xiaobin Wang

doi:10.1038/ncomms7304

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

Xiumei Hong, Ke Hao, Christine Ladd-Acosta, Kasper D. Hansen, Hui Ju Tsai, Xin Liu, Xin Xu, Timothy A. Thornton, Deanna Caruso, Corinne A. Keet, Yifei Sun, Guoying Wang, Wei Luo, Rajesh Kumar, Ramsay Fuleihan, Anne Marie Singh, Jennifer S. Kim, Rachel E. Story, Ruchi S. Gupta, Peisong GaoZhu Chen, Sheila O. Walker, Tami R. Bartell, Terri H. Beaty, M. Daniele Fallin, Robert Schleimer, Patrick G. Holt, Kari Christine Nadeau, Robert A. Wood, Jacqueline A. Pongracic, Daniel E. Weeks, Xiaobin Wang^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

204 Scopus citations

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.

Original language	English (US)
Article number	6304
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms7304
State	Published - Mar 2015

Funding

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.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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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., ... Wang, X. (2015). Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children. Nature communications, 6, Article 6304. https://doi.org/10.1038/ncomms7304

@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",

year = "2015",

month = mar,

doi = "10.1038/ncomms7304",

language = "English (US)",

volume = "6",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

}

Hong, 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 2015, 'Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children', Nature communications, vol. 6, 6304. https://doi.org/10.1038/ncomms7304

TY - JOUR

T1 - Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children

AU - Hong, Xiumei

AU - Hao, Ke

AU - Ladd-Acosta, Christine

AU - Hansen, Kasper D.

AU - Tsai, Hui Ju

AU - Liu, Xin

AU - Xu, Xin

AU - Thornton, Timothy A.

AU - Caruso, Deanna

AU - Keet, Corinne A.

AU - Sun, Yifei

AU - Wang, Guoying

AU - Luo, Wei

AU - Kumar, Rajesh

AU - Fuleihan, Ramsay

AU - Singh, Anne Marie

AU - Kim, Jennifer S.

AU - Story, Rachel E.

AU - Gupta, Ruchi S.

AU - Gao, Peisong

AU - Chen, Zhu

AU - Walker, Sheila O.

AU - Bartell, Tami R.

AU - Beaty, Terri H.

AU - Fallin, M. Daniele

AU - Schleimer, Robert

AU - Holt, Patrick G.

AU - Nadeau, Kari Christine

AU - Wood, Robert A.

AU - Pongracic, Jacqueline A.

AU - Weeks, Daniel E.

AU - Wang, Xiaobin

PY - 2015/3

Y1 - 2015/3

N2 - 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.

AB - 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.

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JO - Nature communications

JF - Nature communications

M1 - 6304

ER -

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

Abstract

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