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. 2017 Oct 20;8(1):1056.
doi: 10.1038/s41467-017-01220-0.

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

Ingo Marenholz  1   2 , Sarah Grosche  1   2 , Birgit Kalb  1   2   3 , Franz Rüschendorf  1 , Katharina Blümchen  4 , Rupert Schlags  5 , Neda Harandi  5 , Mareike Price  6 , Gesine Hansen  6 , Jürgen Seidenberg  7 , Holger Röblitz  8 , Songül Yürek  3 , Sebastian Tschirner  3 , Xiumei Hong  9 , Xiaobin Wang  9 , Georg Homuth  10 , Carsten O Schmidt  11 , Markus M Nöthen  12 , Norbert Hübner  1 , Bodo Niggemann  3 , Kirsten Beyer  3 , Young-Ae Lee  13   14
Affiliations

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

Ingo Marenholz et al. Nat Commun. .

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.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Fig. 1
Fig. 1
Study design of the GWAS on food allergy. Workflow of the GWAS on food allergy is shown including the number of cases and controls, and the P value thresholds used for each study set and phenotype. GOFA German Genetics of Food Allergy Study, HNR Heinz Nixdorf Recall Study, SHIP Study of Health in Pomerania, CFA Chicago Food Allergy Study, QC quality control, FA any food allergy, HE hen’s egg allergy, PN peanut allergy, CM cow’s milk allergy, P D, P R, and P metaD+R, P value in the GOFA discovery set, in the GOFA replication set, and in the meta-analysis of both sets, respectively
Fig. 2
Fig. 2
Association results of the GWAS on food allergy. The results of the GWAS on any food allergy (497 cases vs. 2387 controls) and on food-specific allergies against hen’s egg (288 cases), peanut (220 cases), and cow’s milk (169 cases) are presented. The Manhattan plots show the chromosomal positions (x-axis) and association P values (y-axis) for all SNPs of the discovery set. Red and blue lines indicate the thresholds for genome-wide significance (P < 5 × 10−8) and for entering the replication phase (P < 1 × 10−3) respectively
See this image and copyright information in PMC

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