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

Ferreira, Manuel A., McRae, Allan F., Medland, Sarah E., Nyholt, Dale R., Gordon, Scott D., Wright, Margaret J., Henders, Anjali K., Madden, Pamela A.F., Visscher, Peter M., Wray, Naomi R., Heath, Andrew C., Montgomery, Grant W., Duffy, David L., & 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), pp. 458-464.

View at publisher


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 x 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 x 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 x 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.

Impact and interest:

53 citations in Scopus
50 citations in Web of Science®
Search Google Scholar™

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

ID Code: 91921
Item Type: Journal Article
Refereed: Yes
Keywords: Asthma/*epidemiology/*genetics, Australia/epidemiology, Chromosomes, Human, Pair 17/genetics, Cyclic Nucleotide Phosphodiesterases, Type 3/genetics, Cyclic Nucleotide Phosphodiesterases, Type 4, DNA Copy Number Variations, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Membrane Proteins/*genetics, Polymorphism, Single Nucleotide, Receptors, Cell Surface/*genetics, Sequence Deletion/genetics
DOI: 10.1038/ejhg.2010.191
ISSN: 1476-5438
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 14 Jan 2016 23:19
Last Modified: 26 Jun 2017 19:01

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page