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Replication of genomewide associations with allergic sensitization And allergic rhinitis

Nilsson, D.; Henmyr, V.; Hallden, C.; Säll, Torbjörn LU ; Kull, I.; Wickman, M.; Melen, E. and Cardell, L. O. (2014) In Allergy 69(11). p.1506-1514
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
age-dependent effect, allergic rhinitis, allergic sensitization, association study, TLR6-TLR1 locus
in
Allergy
volume
69
issue
11
pages
1506 - 1514
publisher
Wiley-Blackwell
external identifiers
  • wos:000343851200009
  • scopus:84907900926
ISSN
1398-9995
DOI
10.1111/all.12495
language
English
LU publication?
yes
id
1355e442-1c12-49ef-851e-f563be56d208 (old id 4875994)
date added to LUP
2015-01-07 10:30:44
date last changed
2017-09-10 04:18:38
@article{1355e442-1c12-49ef-851e-f563be56d208,
  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 ( &lt;= or &gt;8 years of age). Results: Association tests of the 39 SNPs identified 12 SNPs with P-values &lt;0.05 and Q-values &lt;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 &lt;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.},
  author       = {Nilsson, D. and Henmyr, V. and Hallden, C. and Säll, Torbjörn and Kull, I. and Wickman, M. and Melen, E. and Cardell, L. O.},
  issn         = {1398-9995},
  keyword      = {age-dependent effect,allergic rhinitis,allergic sensitization,association study,TLR6-TLR1 locus},
  language     = {eng},
  number       = {11},
  pages        = {1506--1514},
  publisher    = {Wiley-Blackwell},
  series       = {Allergy},
  title        = {Replication of genomewide associations with allergic sensitization And allergic rhinitis},
  url          = {http://dx.doi.org/10.1111/all.12495},
  volume       = {69},
  year         = {2014},
}