Analyses of associations with asthma in four asthma population samples from Canada and Australia

Daley, Denise, Lemire, Mathieu, Akhabir, Loubna, Chan-Yeung, Moira, He, Jian Qing, McDonald, Treena, Sandford, Andrew, Stefanowicz, Dorota, Tripp, Ben, Zamar, David, Bosse, Yohan, Ferretti, Vincent, Montpetit, Alexandre, Tessier, Marie-Catherine, Becker, Allan, Kozyrskyj, Anita L., Beilby, John, McCaskie, Pamela A., Musk, Bill, Warrington, Nicole, James, Alan, Laprise, Catherine, Palmer, Lyle J., Pare, Peter D. and Hudson, Thomas J. (2009) Analyses of associations with asthma in four asthma population samples from Canada and Australia. Human Genetics, 125 4: 445-459. doi:10.1007/s00439-009-0643-8

Author Daley, Denise
Lemire, Mathieu
Akhabir, Loubna
Chan-Yeung, Moira
He, Jian Qing
McDonald, Treena
Sandford, Andrew
Stefanowicz, Dorota
Tripp, Ben
Zamar, David
Bosse, Yohan
Ferretti, Vincent
Montpetit, Alexandre
Tessier, Marie-Catherine
Becker, Allan
Kozyrskyj, Anita L.
Beilby, John
McCaskie, Pamela A.
Musk, Bill
Warrington, Nicole
James, Alan
Laprise, Catherine
Palmer, Lyle J.
Pare, Peter D.
Hudson, Thomas J.
Title Analyses of associations with asthma in four asthma population samples from Canada and Australia
Journal name Human Genetics   Check publisher's open access policy
ISSN 0340-6717
Publication date 2009-01-01
Year available 2009
Sub-type Article (original research)
DOI 10.1007/s00439-009-0643-8
Volume 125
Issue 4
Start page 445
End page 459
Total pages 15
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Subject 2716 Genetics (clinical)
1311 Genetics
Abstract Asthma, atopy, and related phenotypes are heterogeneous complex traits, with both genetic and environmental risk factors. Extensive research has been conducted and over hundred genes have been associated with asthma and atopy phenotypes, but many of these findings have failed to replicate in subsequent studies. To separate true associations from false positives, candidate genes need to be examined in large well-characterized samples, using standardized designs (genotyping, phenotyping and analysis). In an attempt to replicate previous associations we amalgamated the power and resources of four studies and genotyped 5,565 individuals to conduct a genetic association study of 93 previously associated candidate genes for asthma and related phenotypes using the same set of 861 single-nucleotide polymorphisms (SNPs), a common genotyping platform, and relatively harmonized phenotypes. We tested for association between SNPs and the dichotomous outcomes of asthma, atopy, atopic asthma, and airway hyperresponsiveness using a general allelic likelihood ratio test. No SNP in any gene reached significance levels that survived correction for all tested SNPs, phenotypes, and genes. Even after relaxing the usual stringent multiple testing corrections by performing a gene-based analysis (one gene at a time as if no other genes were typed) and by stratifying SNPs based on their prior evidence of association, no genes gave strong evidence of replication. There was weak evidence to implicate the following: IL13, IFNGR2, EDN1, and VDR in asthma; IL18, TBXA2R, IFNGR2, and VDR in atopy; TLR9, TBXA2R, VDR, NOD2, and STAT6 in airway hyperresponsiveness; TLR10, IFNGR2, STAT6, VDR, and NPSR1 in atopic asthma. Additionally we found an excess of SNPs with small effect sizes (OR < 1.4). The low rate of replication may be due to small effect size, differences in phenotypic definition, differential environmental effects, and/or genetic heterogeneity. To aid in future replication studies of asthma genes a comprehensive database was compiled and is available to the scientific community at
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: UQ Diamantina Institute Publications
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Created: Wed, 11 Jun 2014, 02:30:42 EST by Kylie Hengst on behalf of UQ Diamantina Institute