Genome-wide association study reveals an association between the HLA-DPB1*02:01:02 allele and wheat-dependent exercise-induced anaphylaxis

摘要

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 x 10(-8)). The HLA-DPB1*02:01:02 allele displayed the most significant association with WDEIA (OR = 4.51 95 CI, 2.66-7.63, p = 2.28 x 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 x 10(-8)). Ameta-analysis performed in the combined set revealed that the HLA-DPB1*02:01:02 allele was significantly associated with an increased risk of WDEIA (OR = 4.13 95 CI, 2.89-5.93, p = 1.06 x 10(-14)). Individuals carrying the HLA-DPB1*02:01:02 allele have a significantly increased risk of WDEIA. Further validation of these findings in independent multiethnic cohorts is needed.