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

Nat Commun. 2015 Feb 24:6:6304. doi: 10.1038/ncomms7304.

Authors

Xiumei Hong¹, Ke Hao², Christine Ladd-Acosta³, Kasper D Hansen⁴, Hui-Ju Tsai⁵, Xin Liu⁶, Xin Xu⁷, Timothy A Thornton⁸, Deanna Caruso¹, Corinne A Keet⁹, Yifei Sun¹⁰, Guoying Wang¹, Wei Luo¹¹, Rajesh Kumar¹², Ramsay Fuleihan¹², Anne Marie Singh¹³, Jennifer S Kim¹⁴, Rachel E Story¹⁵, Ruchi S Gupta¹⁶, Peisong Gao¹⁷, Zhu Chen¹, Sheila O Walker¹, Tami R Bartell¹⁶, Terri H Beaty³, M Daniele Fallin¹⁸, Robert Schleimer¹⁹, Patrick G Holt²⁰, Kari Christine Nadeau²¹, Robert A Wood²², Jacqueline A Pongracic¹², Daniel E Weeks²³, Xiaobin Wang²⁴

Affiliations

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 Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
³ Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205, USA.
⁴ 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.
⁵ 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.
⁶ 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.
⁷ Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou 510515, China.
⁸ Department of Biostatistics, University of Washington, Seattle, Washington 98195, USA.
⁹ 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.
¹⁰ Department of Biostatistics, Johns Hopkins University Bloomberg School of Public Health Baltimore, Baltimore, Maryland 21205, USA.
¹¹ 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.
¹² Division of Allergy and Immunology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois 60611, USA.
¹³ Department of Pediatrics and Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern Feinberg School of Medicine, Chicago, Illinois 61611, USA.
¹⁴ 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.
¹⁵ 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.
¹⁶ 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.
¹⁷ Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA.
¹⁸ Department of Mental Health, Wendy Klag Center for Autism and Developmental Disabilities, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.
¹⁹ Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
²⁰ Telethon Kids Institute, University of Western Australia; Perth and Queensland Children's Medical Research Institute, University of Queensland, Brisbane, Queensland 4029, Australia.
²¹ Division of Allergy, Immunology and Rheumatology, Stanford University School of Medicine, Stanford, California 94305, USA.
²² Division of Pediatric Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
²³ Departments of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
²⁴ 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.

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.

Publication types

Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Child
Child, Preschool
DNA Methylation
Epigenesis, Genetic
Female
Genetic Predisposition to Disease
Genome-Wide Association Study*
HLA-DQ Antigens / genetics*
HLA-DR Antigens / genetics*
Humans
Infant
Male
Peanut Hypersensitivity / genetics*
Phenotype
Polymorphism, Single Nucleotide
United States
Young Adult

Substances

HLA-DQ Antigens
HLA-DR Antigens

Abstract

Publication types

MeSH terms

Substances

Grants and funding