Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia

Ferreira, Manuel A. R., McRae, Allan F., Medland, Sarah E., Nyholt, Dale R., Gordon, Scott D., Wright, Margaret J., Henders, Anjali K., Madden, Pamela A., Visscher, Peter M., Wray, Naomi R., Heath, Andrew C., Montgomery, Grant W., Duffy, David L. and Martin, Nicholas G. (2011) Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia. European Journal of Human Genetics, 19 4: 458-464. doi:10.1038/ejhg.2010.191


Author Ferreira, Manuel A. R.
McRae, Allan F.
Medland, Sarah E.
Nyholt, Dale R.
Gordon, Scott D.
Wright, Margaret J.
Henders, Anjali K.
Madden, Pamela A.
Visscher, Peter M.
Wray, Naomi R.
Heath, Andrew C.
Montgomery, Grant W.
Duffy, David L.
Martin, Nicholas G.
Title Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia
Formatted title
Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia
Journal name European Journal of Human Genetics   Check publisher's open access policy
ISSN 1018-4813
1476-5438
Publication date 2011-04
Year available 2010
Sub-type Article (original research)
DOI 10.1038/ejhg.2010.191
Volume 19
Issue 4
Start page 458
End page 464
Total pages 7
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Formatted abstract
Genome-wide association studies followed by replication provide a powerful approach to map genetic risk factors for asthma. We sought to search for new variants associated with asthma and attempt to replicate the association with four loci reported previously (ORMDL3, PDE4D, DENND1B and IL1RL1). Genome-wide association analyses of individual single nucleotide polymorphisms (SNPs), rare copy number variants (CNVs) and overall CNV burden were carried out in 986 asthma cases and 1846 asthma-free controls from Australia. The most-associated locus in the SNP analysis was ORMDL3 (rs6503525, P=4.8 × 10−7). Five other loci were associated with P<10−5, most notably the chemokine CXC motif ligand 14 (CXCL14) gene (rs31263, P=7.8 × 10−6). We found no evidence for association with the specific risk variants reported recently for PDE4D, DENND1B and ILR1L1. However, a variant in IL1RL1 that is in low linkage disequilibrium with that reported previously was associated with asthma risk after accounting for all variants tested (rs10197862, gene wide P=0.01). This association replicated convincingly in an independent cohort (P=2.4 × 10−4). A 300-kb deletion on chromosome 17q21 was associated with asthma risk, but this did not reach experiment-wide significance. Asthma cases and controls had comparable CNV rates, length and number of genes affected by deletions or duplications. In conclusion, we confirm the association between asthma risk and variants in ORMDL3 and identify a novel risk variant in IL1RL1. Follow-up of the 17q21 deletion in larger cohorts is warranted.
Keyword Whole-genome
Gene
Atopy
Heterogeneity
Structural
IKZF3
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: Tue, 02 Apr 2013, 13:37:32 EST by Allan Mcrae on behalf of UQ Diamantina Institute