Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype

Ferreira, Manuel A.R., Matheson, Melanie C., Tang, Clara S., Granell, Raquel, Ang, Wei, Hui, Jennie, Kiefer, Amy K., Duffy, David L., Baltic, Svetlana, Danoy, Patrick, Bui, Minh, Price, Loren, Sly, Peter D., Eriksson, Nicholas, Madden, Pamela A., Abramson, Michael J., Holt, Patrick G., Heath, Andrew C., Hunter, Michael, Musk, Bill, Robertson, Colin F., Le Souëf, Peter, Montgomery, Grant W., Henderson, A. John, Tung, Joyce Y., Dharmage, Shyamali C., Brown, Matthew A., James, Alan, Thompson, Philip J., Pennell, Craig, Martin, Nicholas G., Evans, David M., Hinds, David A., & Hopper, John L. (2014) Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype. Journal of Allergy and Clinical Immunology, 133(6), pp. 1564-1571.

View at publisher

Abstract

Background

To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever.

Objective

We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases.

Methods

We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091).

Results

At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10−9) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10−8). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10−7) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10−6).

Conclusion

By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency.

Impact and interest:

45 citations in Scopus
Search Google Scholar™
42 citations in Web of Science®

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: 89224
Item Type: Journal Article
Refereed: Yes
Keywords: Rhinitis; atopy; selection; genetic correlation; bivariate; single nucleotide polymorphism
DOI: 10.1016/j.jaci.2013.10.030
ISSN: 0091-6749
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Funding:
Deposited On: 16 Oct 2015 00:41
Last Modified: 16 Feb 2016 05:23

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page