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.
authors.affiliation: Department of Population, 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.
authors.forename: Xiumei
authors.initials: X
authors.lastname: Hong
authors.affiliation: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Hao
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Ladd-Acosta
authors.affiliation: 1] Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health Baltimore, Baltimore, Maryland 21205, USA [2] McKusick-Nathans Insitute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Kasper D
authors.initials: KD
authors.lastname: Hansen
authors.affiliation: 1] Mary Ann and J. Milburn Smith Child Health Research Program, Department of Pediatrics, Northwestern University Feinberg School of Medicine and Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, USA [2] Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, Zhunan 35053, Taiwan [3] Department of Public Health, China Medical University, Taichung 40402, Taiwan.
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Tsai
authors.affiliation: 1] Mary Ann and J. Milburn Smith Child Health Research Program, Department of Pediatrics, Northwestern University Feinberg School of Medicine and Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, USA [2] Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Thornton
authors.affiliation: Department of Population, 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.
authors.forename: Deanna
authors.initials: D
authors.lastname: Caruso
authors.affiliation: 1] Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA [2] Division of Pediatric Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Corinne A
authors.initials: CA
authors.lastname: Keet
authors.affiliation: Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health Baltimore, Baltimore, Maryland 21205, USA.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Population, 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.
authors.forename: Guoying
authors.initials: G
authors.lastname: Wang
authors.affiliation: 1] Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA [2] College of Computer Science and Technology, Huaqiao University, Xiamen 361021, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.affiliation: Division of Allergy and Immunology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, USA.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Division of Allergy and Immunology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, USA.
authors.forename: Ramsay
authors.initials: R
authors.lastname: Fuleihan
authors.affiliation: Department of Pediatrics and Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern Feinberg School of Medicine, Chicago, Illinois 61611, USA.
authors.forename: Anne Marie
authors.initials: AM
authors.lastname: Singh
authors.affiliation: 1] Division of Allergy and Immunology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, USA [2] NorthShore University HealthSystem, Evanston, Illinois 60201, USA.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Kim
authors.affiliation: 1] Division of Allergy and Immunology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, USA [2] NorthShore University Health Systems, Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Story
authors.affiliation: Mary Ann and J. Milburn Smith Child Health Research Program, Department of Pediatrics, Northwestern University Feinberg School of Medicine and Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, USA.
authors.forename: Ruchi S
authors.initials: RS
authors.lastname: Gupta
authors.affiliation: Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
authors.forename: Peisong
authors.initials: P
authors.lastname: Gao
authors.affiliation: Department of Population, 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.
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Population, 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.
authors.forename: Sheila O
authors.initials: SO
authors.lastname: Walker
authors.affiliation: Mary Ann and J. Milburn Smith Child Health Research Program, Department of Pediatrics, Northwestern University Feinberg School of Medicine and Stanley Manne Children's Research Institute, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, USA.
authors.forename: Tami R
authors.initials: TR
authors.lastname: Bartell
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
authors.affiliation: Department of Mental Health, Wendy Klag Center for Autism and Developmental Disabilities, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
authors.forename: M Daniele
authors.initials: MD
authors.lastname: Fallin
authors.affiliation: Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Schleimer
authors.affiliation: Telethon Kids Institute, University of Western Australia; Perth and Queensland Children's Medical Research Institute, University of Queensland, Brisbane, Queensland 4029, Australia.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
authors.affiliation: Division of Allergy, Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California 94305, USA.
authors.forename: Kari Christine
authors.initials: KC
authors.lastname: Nadeau
authors.affiliation: Division of Pediatric Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wood
authors.affiliation: Division of Allergy and Immunology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, USA.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Pongracic
authors.affiliation: Departments of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Weeks
authors.affiliation: 1] Department of Population, 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 [2] Division of General Pediatrics and Adolescent Medicine, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D021183:Peanut Hypersensitivity / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014481:United States; D055815:Young Adult
chemical_list: D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens