Genome-wide association study identifies the SERPINB gene cluster as a susceptibility locus for food allergy

Ingo Marenholz, Sarah Grosche, Birgit Kalb, Franz Rüschendorf, Katharina Blümchen, Rupert Schlags, Neda Harandi, Mareike Price, Gesine Hansen, Jürgen Seidenberg, Holger Röblitz, Songül Yürek, Sebastian Tschirner, Xiumei Hong, Xiaobin Wang, Georg Homuth, Carsten O. Schmidt, Markus M. Nöthen, Norbert Hübner, Bodo Niggemann, Kirsten Beyer and Young-Ae Lee ()
Additional contact information
Ingo Marenholz: Max-Delbrück-Center (MDC) for Molecular Medicine
Sarah Grosche: Max-Delbrück-Center (MDC) for Molecular Medicine
Birgit Kalb: Max-Delbrück-Center (MDC) for Molecular Medicine
Franz Rüschendorf: Max-Delbrück-Center (MDC) for Molecular Medicine
Katharina Blümchen: Pulmonology and Cystic Fibrosis, Children’s Hospital, Goethe University
Rupert Schlags: Wangen Hospital
Neda Harandi: Wangen Hospital
Mareike Price: Allergology and Neonatology, Hannover Medical School
Gesine Hansen: Allergology and Neonatology, Hannover Medical School
Jürgen Seidenberg: Neonatology and Intensive Care, Medical Campus of University Oldenburg
Holger Röblitz: Sana Klinikum Lichtenberg
Songül Yürek: Charité University Medical Center
Sebastian Tschirner: Charité University Medical Center
Xiumei Hong: Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health
Xiaobin Wang: Family and Reproductive Health, Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health
Georg Homuth: Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald
Carsten O. Schmidt: Institute for Community Medicine, Study of Health in Pomerania/KEF, University Medicine Greifswald
Markus M. Nöthen: Life & Brain Center, University of Bonn
Norbert Hübner: Max-Delbrück-Center (MDC) for Molecular Medicine
Bodo Niggemann: Charité University Medical Center
Kirsten Beyer: Charité University Medical Center
Young-Ae Lee: Max-Delbrück-Center (MDC) for Molecular Medicine

Nature Communications, 2017, vol. 8, issue 1, 1-10

Abstract: 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.

Date: 2017
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DOI: 10.1038/s41467-017-01220-0

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