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Abstract
Food allergy is an increasingly important health problem in the world. Several genome-wide association studies (GWAS) focused on European ancestry samples have identified food allergy-specific loci in the HLA class II region. We conducted GWAS of self-reported reactivity with common foods using the data from 11011 Japanese women and identified shrimp and peach allergy-specific loci in the HLA-DR/DQ gene region tagged by rs74995702 (P = 6.30 × 10−17, OR = 1.91) and rs28359884 (P = 2.3 × 10−12, OR = 1.80), respectively. After HLA imputation using a Japanese population-specific reference, the most strongly associated haplotype was HLA-DRB1*04:05-HLA-DQB1*04:01 for shrimp allergy (P = 3.92 × 10−19, OR = 1.99) and HLA-DRB1*09:01-HLA-DQB1*03:03 for peach allergy (P = 1.15 × 10−7, OR = 1.68). Additionally, both allergies’ associated variants were eQTLs for several HLA genes, with HLA-DQA2 the single eQTL gene shared between the two traits. Our study suggests that allergy to certain foods may be related to genetic differences that tag both HLA alleles having particular epitope binding specificities as well as variants modulating expression of particular HLA genes. Investigating this further could increase our understanding of food allergy aetiology and potentially lead to better therapeutic strategies for allergen immunotherapies.
Highlights
Asthma has been traditionally known to be the first wave of the allergy epidemic affecting the lives of millions and is the third leading cause for hospitalization in the United States among people less than 18 years of age[1]
DNA from 11379 female subjects was collected in two study stages (LL01 = 5751, LL02 = 5628), and subjects were queried via questionnaire for putative allergic sensitivity to twenty-seven different foods from fruits, legumes/grains, nuts, vegetables/mushrooms, eggs/dairy, meats, fish, and shellfish product food groups (Supplementary Table S1)
Preliminary genome-wide association studies (GWASs) scans were performed across the 27 foods, and due to noise and a lack of signals for foods with low case sample counts, final GWAS analyses were run across seven foods for which the number of cases were deemed sufficient (>100 cases in both the LL01 and LL02 sample sets; kiwi, peach, Chinese yam, eggs, mackerel, crab, and shrimp in Supplementary Table S1)
Summary
Asthma has been traditionally known to be the first wave of the allergy epidemic affecting the lives of millions and is the third leading cause for hospitalization in the United States among people less than 18 years of age[1]. Food allergy related disorders include acute conditions with the potential to be fatal, along with a number of chronic diseases that mainly occur in the epidermis and gastrointestinal tract[8]. Such disorders can roughly be divided into classical IgE-mediated food allergies or those mediated by other antibody isotypes such as IgA and IgG9. Previous studies have shown that the repertoire of antibodies binding to multiple epitopes within food allergens may correlate with disease status[34], and IgE that recognizes the tertiary allergen structure is often associated with transient childhood allergy while linear epitope recognition often results in persistence allergy into adulthood[34,35]
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