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 NiggemannKirsten Beyer, Young Ae Lee

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number1056
JournalNature communications
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2017

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Marenholz, I., Grosche, S., Kalb, B., Rüschendorf, F., Blümchen, K., Schlags, R., Harandi, N., Price, M., Hansen, G., Seidenberg, J., Röblitz, H., Yürek, S., Tschirner, S., Hong, X., Wang, X., Homuth, G., Schmidt, C. O., Nöthen, M. M., Hübner, N., ... Lee, Y. A. (2017). Genome-wide association study identifies the SERPINB gene cluster as a susceptibility locus for food allergy. Nature communications, 8(1), [1056]. https://doi.org/10.1038/s41467-017-01220-0