A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order

Ramasamy, Adaikalavan, Curjuric, Ivan, Coin, Lachlan J., Kumar, Ashish, McArdle, Wendy L., Imboden, Medea, Leynaert, Benedicte, Kogevinas, Manolis, Schmid-Grendelmeier, Peter, Pekkanen, Juha, Wjst, Matthias, Bircher, Andreas J., Sovio, Ulla, Rochat, Thierry, Hartikainen, Anna-Liisa, Balding, David J., Jarvelin, Marjo-Riitta, Probst-Hensch, Nicole, Strachan, David P. and Jarvis, Deborah L. (2011) A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order. Journal of Allergy and Clinical Immunology, 128 5: 996-1005. doi:10.1016/j.jaci.2011.08.030

Author Ramasamy, Adaikalavan
Curjuric, Ivan
Coin, Lachlan J.
Kumar, Ashish
McArdle, Wendy L.
Imboden, Medea
Leynaert, Benedicte
Kogevinas, Manolis
Schmid-Grendelmeier, Peter
Pekkanen, Juha
Wjst, Matthias
Bircher, Andreas J.
Sovio, Ulla
Rochat, Thierry
Hartikainen, Anna-Liisa
Balding, David J.
Jarvelin, Marjo-Riitta
Probst-Hensch, Nicole
Strachan, David P.
Jarvis, Deborah L.
Title A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order
Journal name Journal of Allergy and Clinical Immunology   Check publisher's open access policy
ISSN 0091-6749
Publication date 2011-01-01
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.jaci.2011.08.030
Open Access Status Not yet assessed
Volume 128
Issue 5
Start page 996
End page 1005
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher Mosby
Language eng
Formatted abstract
Background: Hay fever or seasonal allergic rhinitis (AR) is a chronic disorder associated with IgE sensitization to grass. The underlying genetic variants have not been studied comprehensively. There is overwhelming evidence that those who have older siblings have less AR, although the mechanism for this remains unclear.

Objective: We sought to identify common genetic variant associations with prevalent AR and grass sensitization using existing genome-wide association study (GWAS) data and to determine whether genetic variants modify the protective effect of older siblings.

Method: Approximately 2.2 million genotyped or imputed single nucleotide polymorphisms were investigated in 4 large European adult cohorts for AR (3,933 self-reported cases vs 8,965 control subjects) and grass sensitization (2,315 cases vs 10,032 control subjects).

Results: Three loci reached genome-wide significance for either phenotype. The HLA variant rs7775228, which cis-regulates HLA-DRB4, was strongly associated with grass sensitization and weakly with AR (P grass = 1.6 × 10 -9; P AR = 8.0 × 10 -3). Variants in a locus near chromosome 11 open reading frame 30 (C11orf30) and leucine-rich repeat containing 32 (LRRC32), which was previously associated with atopic dermatitis and eczema, were also strongly associated with both phenotypes (rs2155219; P grass = 9.4 × 10 -9; P AR = 3.8 × 10 -8). The third genome-wide significant variant was rs17513503 (P grass = 1.2 × 10 -8; PAR = 7.4 × 10 -7) which was located near transmembrane protein 232 (TMEM232) and solute carrier family 25, member 46 (SLC25A46). Twelve further loci with suggestive associations were also identified. Using a candidate gene approach, where we considered variants within 164 genes previously thought to be important, we found variants in 3 further genes that may be of interest: thymic stromal lymphopoietin (TSLP), Toll-like receptor 6 (TLR6) and nucleotide-binding oligomerization domain containing 1 (NOD1/CARD4). We found no evidence for variants that modified the effect of birth order on either phenotype.

Conclusions: This relatively large meta-analysis of GWASs identified few loci associated with AR and grass sensitization. No birth order interaction was identified in the current analyses. 
Keyword British 1958 Birth Cohort
European Community Respiratory Health Survey
gene-environment interaction
genome-wide association study
Hay fever
hygiene hypothesis
IgE sensitization to grass
Northern Finland Birth Cohort of 1966
older siblings
Swiss Study on Air Pollution and Lung Disease in Adults
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 018996
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 108 times in Thomson Reuters Web of Science Article | Citations
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