Genome-wide association study reveals an association between the HLA-DPB102:01:02 allele and wheat-dependent exercise-induced anaphylaxis

Koya Fukunaga, Yuko Chinuki, Yuto Hamada, Yuma Fukutomi, Akiko Sugiyama, Reiko Kishikawa, Atsushi Fukunaga, Yoshiko Oda, Tsukasa Ugajin, Hiroo Yokozeki, Naoe Harada, Masataka Suehiro, Michihiro Hide, Yukinobu Nakagawa, Emiko Noguchi, Masashi Nakamura, Kayoko Matsunaga, Akiko Yagami, Eishin Morita, Taisei Mushiroda

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14 Citations (Scopus)


Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a life-threatening food allergy triggered by wheat in combination with the second factor such as exercise. The identification of potential genetic risk factors for this allergy might help high-risk individuals before consuming wheat-containing food. We aimed to identify genetic variants associated with WDEIA. A genome-wide association study was conducted in a discovery set of 77 individuals with WDEIA and 924 control subjects via three genetic models. The associations were confirmed in a replication set of 91 affected individuals and 435 control individuals. Summary statistics from the combined set were analyzed by meta-analysis with a random-effect model. In the discovery set, a locus on chromosome 6, rs9277630, was associated with WDEIA in the dominant model (OR = 3.95 [95% CI, 2.31−6.73], p = 7.87 × 10−8). The HLA-DPB102:01:02 allele displayed the most significant association with WDEIA (OR = 4.51 [95% CI, 2.66−7.63], p = 2.28 × 10−9), as determined via HLA imputation following targeted sequencing. The association of the allele with WDEIA was confirmed in replication samples (OR = 3.82 [95% CI, 2.33−6.26], p = 3.03 × 10−8). A meta-analysis performed in the combined set revealed that the HLA-DPB102:01:02 allele was significantly associated with an increased risk of WDEIA (OR = 4.13 [95% CI, 2.89−5.93], p = 1.06 × 10−14). Individuals carrying the HLA-DPB102:01:02 allele have a significantly increased risk of WDEIA. Further validation of these findings in independent multiethnic cohorts is needed.

Original languageEnglish
Pages (from-to)1540-1548
Number of pages9
JournalAmerican Journal of Human Genetics
Issue number8
Publication statusPublished - 05-08-2021

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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