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 | |
| State | Published - Jan 1 2015 |
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ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
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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 journal › Article
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 - 2015/1/1
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.
UR - http://www.scopus.com/inward/record.url?scp=84923658758&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84923658758&partnerID=8YFLogxK
U2 - 10.1038/ncomms7304
DO - 10.1038/ncomms7304
M3 - Article
C2 - 25710614
AN - SCOPUS:84923658758
VL - 6
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 6304
ER -