Replication of genomewide associations with allergic sensitization and allergic rhinitis
- 6 September 2014
- Vol. 69 (11), 1506-1514
- https://doi.org/10.1111/all.12495
Abstract
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 rhinitisFunding Information
- the Swedish Research Council
This publication has 23 references indexed in Scilit:
- Childhood-to-adolescence evolution of IgE antibodies to pollens and plant foods in the BAMSE cohortJournal of Allergy and Clinical Immunology, 2014
- Meta-analysis of genome-wide association studies identifies ten loci influencing allergic sensitizationNature Genetics, 2013
- A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility lociNature Genetics, 2013
- Poor Reproducibility of Allergic Rhinitis SNP AssociationsPLOS ONE, 2013
- Development and comorbidity of eczema, asthma and rhinitis to age 12 – data from the BAMSE birth cohortAllergy, 2012
- A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth orderJournal of Allergy and Clinical Immunology, 2011
- Heritability of Self-Reported Asthma and Allergy: A Study in Adult Dutch Twins, Siblings and ParentsTwin Research and Human Genetics, 2008
- Heritability and Shared Genetic Effects of Asthma and Hay Fever: An Italian Study of Young TwinsTwin Research and Human Genetics, 2008
- PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage AnalysesAmerican Journal of Human Genetics, 2007
- A Direct Approach to False Discovery RatesJournal of the Royal Statistical Society Series B: Statistical Methodology, 2002