Abstract

Genetic factors and mechanisms underlying food allergy are largely unknown. Due to heterogeneity of symptoms a reliable diagnosis is often difficult to make. Here, we report a genome-wide association study on food allergy diagnosed by oral food challenge in 497 cases and 2387 controls. We identify five loci at genome-wide significance, the clade B serpin (SERPINB) gene cluster at 18q21.3, the cytokine gene cluster at 5q31.1, the filaggrin gene, the C11orf30/LRRC32 locus, and the human leukocyte antigen (HLA) region. Stratifying the results for the causative food demonstrates that association of the HLA locus is peanut allergy-specific whereas the other four loci increase the risk for any food allergy. Variants in the SERPINB gene cluster are associated with SERPINB10 expression in leukocytes. Moreover, SERPINB genes are highly expressed in the esophagus. All identified loci are involved in immunological regulation or epithelial barrier function, emphasizing the role of both mechanisms in food allergy.

Details

Title
Genome-wide association study identifies the SERPINB gene cluster as a susceptibility locus for food allergy
Author
Marenholz, Ingo 1 ; Grosche, Sarah 1 ; Kalb, Birgit 2 ; Rüschendorf, Franz 3   VIAFID ORCID Logo  ; Blümchen, Katharina 4 ; Schlags, Rupert 5 ; Harandi, Neda 5 ; Price, Mareike 6 ; Hansen, Gesine 6 ; Seidenberg, Jürgen 7 ; Röblitz, Holger 8 ; Yürek, Songül 9 ; Tschirner, Sebastian 9 ; Hong, Xiumei 10 ; Wang, Xiaobin 10 ; Homuth, Georg 11 ; Schmidt, Carsten O 12 ; Nöthen, Markus M 13 ; Hübner, Norbert 3 ; Niggemann, Bodo 9 ; Beyer, Kirsten 9 ; Young-Ae, Lee 1 

1  Max-Delbrück-Center (MDC) for Molecular Medicine, Berlin, Germany; Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité University Medical Center, Berlin, Germany 
2  Max-Delbrück-Center (MDC) for Molecular Medicine, Berlin, Germany; Clinic for Pediatric Allergy, Experimental and Clinical Research Center, Charité University Medical Center, Berlin, Germany; Department of Pediatric Pneumology and Immunology, Charité University Medical Center, Berlin, Germany 
3  Max-Delbrück-Center (MDC) for Molecular Medicine, Berlin, Germany 
4  Department of Allergy, Pulmonology and Cystic Fibrosis, Children’s Hospital, Goethe University, Frankfurt am Main, Germany 
5  Department of Pediatric Pneumology and Allergology, Wangen Hospital, Wangen, Germany 
6  Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany 
7  Department of Pediatric Pneumology and Allergology, Neonatology and Intensive Care, Medical Campus of University Oldenburg, Oldenburg, Germany 
8  Department of Pediatrics and Adolescent Medicine, Sana Klinikum Lichtenberg, Berlin, Germany 
9  Department of Pediatric Pneumology and Immunology, Charité University Medical Center, Berlin, Germany 
10  Department of Population, Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA 
11  Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany 
12  Institute for Community Medicine, Study of Health in Pomerania/KEF, University Medicine Greifswald, Greifswald, Germany 
13  Institute of Human Genetics and Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany 
Pages
1-10
Publication year
2017
Publication date
Oct 2017
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-017-01220-0
ProQuest document ID
1953074611
Copyright
© 2017. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.