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 & 12 others 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*

*Corresponding author for this work

Research output: Contribution to journalArticle

90 Citations (Scopus)

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 languageEnglish (US)
Article number6304
JournalNature communications
Volume6
DOIs
StatePublished - Jan 1 2015

Fingerprint

Peanut Hypersensitivity
Allergies
mediation
Food Hypersensitivity
genome
Genome-Wide Association Study
loci
food
Epigenomics
genes
HLA-DQ Antigens
methylation
Genes
polymorphism
nucleotides
HLA-DR Antigens
DNA Methylation
Single Nucleotide Polymorphism
deoxyribonucleic acid
HLA-DRB1 Chains

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Hong, Xiumei ; Hao, Ke ; Ladd-Acosta, Christine ; Hansen, Kasper D. ; Tsai, Hui Ju ; Liu, Xin ; Xu, Xin ; Thornton, Timothy A. ; Caruso, Deanna ; Keet, Corinne A. ; Sun, Yifei ; Wang, Guoying ; Luo, Wei ; Kumar, Rajesh ; Fuleihan, Ramsay ; Singh, Anne Marie ; Kim, Jennifer S. ; Story, Rachel E. ; Gupta, Ruchi S. ; Gao, Peisong ; Chen, Zhu ; Walker, Sheila O. ; Bartell, Tami R. ; Beaty, Terri H. ; Fallin, M. Daniele ; Schleimer, Robert ; Holt, Patrick G. ; Nadeau, Kari Christine ; Wood, Robert A. ; Pongracic, Jacqueline A. ; Weeks, Daniel E. ; Wang, Xiaobin. / Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children. In: Nature communications. 2015 ; Vol. 6.
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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",
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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

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

In: Nature communications, Vol. 6, 6304, 01.01.2015.

Research output: Contribution to journalArticle

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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 - 2015/1/1

Y1 - 2015/1/1

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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