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 and Xiaobin Wang ()
Additional contact information
Xiumei Hong: Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, E4132, Baltimore, Maryland 21205, USA
Ke Hao: Icahn School of Medicine at Mount Sinai
Christine Ladd-Acosta: Johns Hopkins University Bloomberg School of Public Health
Kasper D. Hansen: Johns Hopkins University Bloomberg School of Public Health Baltimore
Hui-Ju Tsai: Mary Ann and J. Milburn Smith Child Health Research Program, Northwestern University Feinberg School of Medicine and Stanley Manne Children’s Research Institute, Ann and Robert H. Lurie Children’s Hospital of Chicago
Xin Liu: Mary Ann and J. Milburn Smith Child Health Research Program, Northwestern University Feinberg School of Medicine and Stanley Manne Children’s Research Institute, Ann and Robert H. Lurie Children’s Hospital of Chicago
Xin Xu: Guangdong Provincial Institute of Nephrology, Southern Medical University
Timothy A. Thornton: University of Washington
Deanna Caruso: Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, E4132, Baltimore, Maryland 21205, USA
Corinne A. Keet: Johns Hopkins University Bloomberg School of Public Health
Yifei Sun: Johns Hopkins University Bloomberg School of Public Health Baltimore
Guoying Wang: Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, E4132, Baltimore, Maryland 21205, USA
Wei Luo: Icahn School of Medicine at Mount Sinai
Rajesh Kumar: Ann and Robert H. Lurie Children’s Hospital of Chicago
Ramsay Fuleihan: Ann and Robert H. Lurie Children’s Hospital of Chicago
Anne Marie Singh: Ann and Robert H. Lurie Children’s Hospital of Chicago, Northwestern Feinberg School of Medicine
Jennifer S. Kim: Ann and Robert H. Lurie Children’s Hospital of Chicago
Rachel E. Story: Ann and Robert H. Lurie Children’s Hospital of Chicago
Ruchi S. Gupta: Mary Ann and J. Milburn Smith Child Health Research Program, Northwestern University Feinberg School of Medicine and Stanley Manne Children’s Research Institute, Ann and Robert H. Lurie Children’s Hospital of Chicago
Peisong Gao: Johns Hopkins University School of Medicine
Zhu Chen: Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, E4132, Baltimore, Maryland 21205, USA
Sheila O. Walker: Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, E4132, Baltimore, Maryland 21205, USA
Tami R. Bartell: Mary Ann and J. Milburn Smith Child Health Research Program, Northwestern University Feinberg School of Medicine and Stanley Manne Children’s Research Institute, Ann and Robert H. Lurie Children’s Hospital of Chicago
Terri H. Beaty: Johns Hopkins University Bloomberg School of Public Health
M. Daniele Fallin: Wendy Klag Center for Autism and Developmental Disabilities, Bloomberg School of Public Health, Johns Hopkins University
Robert Schleimer: Northwestern University Feinberg School of Medicine
Patrick G. Holt: Telethon Kids Institute, University of Western Australia
Kari Christine Nadeau: Immunology and Rheumatology, Stanford University School of Medicine
Robert A. Wood: Johns Hopkins University School of Medicine
Jacqueline A. Pongracic: Ann and Robert H. Lurie Children’s Hospital of Chicago
Daniel E. Weeks: Graduate School of Public Health, University of Pittsburgh
Xiaobin Wang: Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, E4132, Baltimore, Maryland 21205, USA

Nature Communications, 2015, vol. 6, issue 1, 1-12

Abstract: 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

Date: 2015
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DOI: 10.1038/ncomms7304

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