A Canadian genome-wide association study and meta-analysis confirm HLA as a risk factor for peanut allergy independent of asthma

To the Editor: Previously, we identified the HLA region as a risk factor for peanut allergy (PA); this observation is supported further by 2 independent genome-wide association studies (GWASs).1,2 The HLA class II genes (including HLA-DR, HLA-DQ, and HLA-DP) encode molecules involved in presentation of extracellular antigens, such as peanut allergens, to T lymphocytes, which in turn mediates B-cell antibody production. Detailed methods, including PA inclusion criteria (see Table E1 in this article's Online Repository at www.jacionline.org), quality control, and imputation, were published previously (see Figs E1 and E2 in this article's Online Repository at www.jacionline.org).4 In addition to the CanPAR GWAS, 6 additional studies were included in a meta-analysis of the HLA region: 2 American studies (the Chicago Food Allergy study [n = 2,197; 316 PA cases])1 and the Genetic Epidemiology Research on Aging (GERA) cohort (n = 29,053; 5108 self-reported food allergy]),5 the Australian HealthNuts study (n = 221; 73 PA cases),2 and the German Understanding Food Allergy study (n = 2,592; 205 PA cases).2 Genotyping for HLA SNPs was conducted in Dutch subjects from 2 studies: IDEAL and GENEVA (n = 1,512; 138 PA cases). Both the IDEAL and GENEVA studies include cases of general food allergy.6 See Table E2 in this article's Online Repository at www.jacionline.org for study and phenotype descriptions.4 Fixed- and random-effects models evaluate heterogeneity and require point estimates. Because the Chicago Food Allergy and Understanding Food Allergy studies provided P value and sample sizes only, for meta-analyses, P values were obtained by using the Stouffer weighted z score. The presence of genetic risk factors for multiple atopic conditions within HLA, all at genome-wide significance, and our results demonstrating that HLA-DQB1 SNPs identified in CanPAR are independent of asthma and numerous eQTLs identified in the region suggest that this region is associated with the cause of several allergic phenotypes.