Association and interaction analyses of eight genes under asthma linkage peaks

Ferreira, M. A. R., Zhao, Z. Z., Thomsen, S. F., James, M., Evans, D. M., Postmus, P. E., Kyvik, K. O., Backer, V., Boomsma, D. I., Martin, N. G., Montgomery, G. W. and Duffy, D. L. (2009) Association and interaction analyses of eight genes under asthma linkage peaks. Allergy, 64 11: 1623-1628. doi:10.1111/j.1398-9995.2009.02091.x


Author Ferreira, M. A. R.
Zhao, Z. Z.
Thomsen, S. F.
James, M.
Evans, D. M.
Postmus, P. E.
Kyvik, K. O.
Backer, V.
Boomsma, D. I.
Martin, N. G.
Montgomery, G. W.
Duffy, D. L.
Title Association and interaction analyses of eight genes under asthma linkage peaks
Journal name Allergy   Check publisher's open access policy
ISSN 0105-4538
Publication date 2009-10-08
Sub-type Article (original research)
DOI 10.1111/j.1398-9995.2009.02091.x
Open Access Status
Volume 64
Issue 11
Start page 1623
End page 1628
Total pages 6
Editor J. Bousquet
Place of publication United Kingdom
Publisher Wiley-Blackwell Publishing
Collection year 2010
Language eng
Subject C1
Formatted abstract
Background: Linkage studies have implicated the 2q33, 9p21, 11q13 and 20q13 regions in the regulation of allergic disease. The aim of this study was to test genetic variants in candidate genes from these regions for association with specific asthma traits.

Methods: Ninety-five single nucleotide polymorphisms (SNP) located in eight genes (CD28, CTLA4, ICOS, ADAM23, ADAMTSL1, MS4A2, CDH26 and HRH3) were genotyped in >5000 individuals from Australian (n = 1162), Dutch (n = 99) and Danish (n = 303) families. Traits tested included doctor-diagnosed asthma, atopy, airway obstruction, total serum immunoglobulin (Ig) E levels and eosinophilia. Association was tested using both multivariate and univariate methods, with gene-wide thresholds for significance determined through simulation. Gene-by-gene and gene-by-environment analyses were also performed.

Results: There was no overall evidence for association with seven of the eight genes tested when considering all genetic variation assayed in each gene. The exception was MS4A2 on chromosome 11q13, which showed weak evidence for association with IgE (gene-wide P < 0.05, rs502581). There were no significant gene-by-gene or gene-by-environment interaction effects after accounting for the number of tests performed.

Conclusions
: The individual variants genotyped in the 2q33, 9p21 and 20q13 regions do not explain a large fraction of the variation in the quantitative traits tested or have a major impact on asthma or atopy risk. Our results are consistent with a weak effect of MS4A2 polymorphisms on the variation of total IgE levels.

Keyword allergy
genome
epistasis
candidate
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
Institute for Molecular Bioscience - Publications
 
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Created: Mon, 29 Mar 2010, 13:27:01 EST by Amanda Jones on behalf of Medicine - Royal Brisbane and Women's Hospital