TY - JOUR
T1 - Genome-wide association study identifies the SERPINB gene cluster as a susceptibility locus for food allergy
AU - Marenholz, Ingo
AU - Grosche, Sarah
AU - Kalb, Birgit
AU - Rüschendorf, Franz
AU - Blümchen, Katharina
AU - Schlags, Rupert
AU - Harandi, Neda
AU - Price, Mareike
AU - Hansen, Gesine
AU - Seidenberg, Jürgen
AU - Röblitz, Holger
AU - Yürek, Songül
AU - Tschirner, Sebastian
AU - Hong, Xiumei
AU - Wang, Xiaobin
AU - Homuth, Georg
AU - Schmidt, Carsten O.
AU - Nöthen, Markus M.
AU - Hübner, Norbert
AU - Niggemann, Bodo
AU - Beyer, Kirsten
AU - Lee, Young Ae
N1 - Funding Information:
We thank Christina Flachmeier, Theresa Thuß for excellent technical assistance, and Sylke Rietz and Marieke Hillen for sample collection and data management. SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grant nos. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED) funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41467-017-01220-0
DO - 10.1038/s41467-017-01220-0
M3 - Article
C2 - 29051540
AN - SCOPUS:85031934909
SN - 2041-1723
VL - 8
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 1056
ER -