Replication of genomewide associations with allergic sensitization And allergic rhinitis

Background: Three genomewide metastudies have recently reported associations with self-reported allergic rhinitis and allergic sensitization. The three studies together identified a set of 37 loci but showed low concordance. This study investigates the reproducibility of the detected single nucleotide polymorphism (SNP) associations in an extensively characterized longitudinal cohort, BAMSE. Methods: Phenotypic evaluation of allergic rhinitis (AR) and allergic sensitization was performed on 2153 children from BAMSE at 8 and 16 years of age. Allele frequencies of 39 SNPs were investigated for association with the exact allergic phenotypes of the metastudies. Odds ratios and false discovery rates were calculated, and the impact of asthma was evaluated. The cases were also evaluated for age at onset effects ( <= or >8 years of age). Results: Association tests of the 39 SNPs identified 12 SNPs with P-values <0.05 and Q-values <0.10. Two of the four loci (TLR6-TLR1 and HLA-DQA1-HLA-DQB1) identified in all three original studies were also identified in this study. Three SNPs located in the TLR6-TLR1 locus had the lowest P-values and Q-values <0.1 when using a well-defined AR phenotype. Two loci showed significant age at onset effects, but the effect of asthma on the associations was very limited. Conclusion: The TLR6-TLR1 locus is likely to have a central role in the development of allergic disease. The association between genetic variation in the SSTR1-MIPOL1 and TSLP-SLC25A46 loci and age at onset is the first report of age at onset effects in allergic rhinitis.