Genome-wide association study of self-reported food reactions in Japanese identifies shrimp and peach specific loci in the HLA-DR/DQ gene region

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.

Advances in asthma and allergic disease genetics: Is bigger always better?

“…4,5 Similarly, a relatively small study of asthmatic patients selected to have moderate-to-severe disease 6 revealed more associated loci than larger studies of ''asthma'' in more heterogeneous populations. 13,14 Finally, studies of highly specific food allergies (ie, hydrolyzed wheat protein, 70 shrimp, 72 peach, 72 and peanut 73 ) in relatively small samples provided genome-wide significant associations with variants in the class II HLA region.…”

“…Genes reported in each study are shown in Table I. Asai et al, 73 Dahlin et al, 14 Demenais et al, 13 Ferreira et al, 5 Khor et al, 72 Noguchi et al, 70 Pividori et al, 4 Shrine et al, 6 Waage et al, 21 Zhu et al 22…”

“…A second study by Khor et al 72 examined food allergy for 7 different foods in 2 Japanese female cohorts recruited as part of an industry-initiated women's health care program (''Luna family''). Both cohorts were comprised of between 252 and 563 cases (depending on the specific food allergy based on self-reported allergic food reactions 72 ). Two loci reached genome-wide significance, one in the shrimp allergy GWAS and one in the peach allergy GWAS, both with SNPs in the HLA-DR/DQ gene region.…”

HLA Polymorphisms and Food Allergy Predisposition

“…Moreover, gene expression modifications of related HLA genes (HLA class II in particular) influenced by genetic variants could play an important role in the etiology of FA. 26…”

Exome Sequencing in Gastrointestinal Food Allergy Induced by Multiple Food Protein

“…The study of common variants across the genome by genome-wide association studies found an association with allergies and genetic variations in genes that play crucial roles in immune responses, such as interleukins, genes from the JAK-STAT signalling pathway, or genes that play an important role in skin barrier, such as FLG, which encodes for the filaggrin precursor [1]. They also found that the Human Leukocyte Antigen (HLA) locus plays a major role in immune regulation [4], and it has been significantly associated with multiple immune disorders, including allergic diseases [5,6].…”