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

M.A.R. Ferreira, M.C. Matheson, C.S. Tang, R. Granell, Wei Ang, Jennie Hui, A.K. Kiefer, D.L. Duffy, S. Baltic, P. Danoy, M. Bui, L. Price, P.D. Sly, N. Eriksson, P.A. Madden, M.J. Abramson, Patrick Holt, A.C. Heath, Michael Hunter, Arthur Musk & 14 others C.F. Robertson, Peter Le Souëf, G.W. Montgomery, A.J. Henderson, J.Y. Tung, S.C. Dharmage, M.A. Brown, Alan James, Philip Thompson, Craig Pennell, N.G. Martin, D.M. Evans, D.A. Hinds, J.L. Hopper

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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.

Original languageEnglish
Pages (from-to)1564-1571
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume133
Issue number6
Early online date31 Dec 2013
DOIs
Publication statusPublished - Jun 2014

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Seasonal Allergic Rhinitis
Genome-Wide Association Study
Asthma
Phenotype
Odds Ratio
Single Nucleotide Polymorphism
Longitudinal Studies
Meta-Analysis
Monocytes
Alleles
Genome
Physicians

Cite this

Ferreira, M.A.R. ; Matheson, M.C. ; Tang, C.S. ; Granell, R. ; Ang, Wei ; Hui, Jennie ; Kiefer, A.K. ; Duffy, D.L. ; Baltic, S. ; Danoy, P. ; Bui, M. ; Price, L. ; Sly, P.D. ; Eriksson, N. ; Madden, P.A. ; Abramson, M.J. ; Holt, Patrick ; Heath, A.C. ; Hunter, Michael ; Musk, Arthur ; Robertson, C.F. ; Le Souëf, Peter ; Montgomery, G.W. ; Henderson, A.J. ; Tung, J.Y. ; Dharmage, S.C. ; Brown, M.A. ; James, Alan ; Thompson, Philip ; Pennell, Craig ; Martin, N.G. ; Evans, D.M. ; Hinds, D.A. ; Hopper, J.L. / Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype. In: Journal of Allergy and Clinical Immunology. 2014 ; Vol. 133, No. 6. pp. 1564-1571.
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title = "Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype",
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.",
author = "M.A.R. Ferreira and M.C. Matheson and C.S. Tang and R. Granell and Wei Ang and Jennie Hui and A.K. Kiefer and D.L. Duffy and S. Baltic and P. Danoy and M. Bui and L. Price and P.D. Sly and N. Eriksson and P.A. Madden and M.J. Abramson and Patrick Holt and A.C. Heath and Michael Hunter and Arthur Musk and C.F. Robertson and {Le Sou{\"e}f}, Peter and G.W. Montgomery and A.J. Henderson and J.Y. Tung and S.C. Dharmage and M.A. Brown and Alan James and Philip Thompson and Craig Pennell and N.G. Martin and D.M. Evans and D.A. Hinds and J.L. Hopper",
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Ferreira, MAR, Matheson, MC, Tang, CS, Granell, R, Ang, W, Hui, J, Kiefer, AK, Duffy, DL, Baltic, S, Danoy, P, Bui, M, Price, L, Sly, PD, Eriksson, N, Madden, PA, Abramson, MJ, Holt, P, Heath, AC, Hunter, M, Musk, A, Robertson, CF, Le Souëf, P, Montgomery, GW, Henderson, AJ, Tung, JY, Dharmage, SC, Brown, MA, James, A, Thompson, P, Pennell, C, Martin, NG, Evans, DM, Hinds, DA & Hopper, JL 2014, 'Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype' Journal of Allergy and Clinical Immunology, vol. 133, no. 6, pp. 1564-1571. https://doi.org/10.1016/j.jaci.2013.10.030

Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype. / Ferreira, M.A.R.; Matheson, M.C.; Tang, C.S.; Granell, R.; Ang, Wei; Hui, Jennie; Kiefer, A.K.; Duffy, D.L.; Baltic, S.; Danoy, P.; Bui, M.; Price, L.; Sly, P.D.; Eriksson, N.; Madden, P.A.; Abramson, M.J.; Holt, Patrick; Heath, A.C.; Hunter, Michael; Musk, Arthur; Robertson, C.F.; Le Souëf, Peter; Montgomery, G.W.; Henderson, A.J.; Tung, J.Y.; Dharmage, S.C.; Brown, M.A.; James, Alan; Thompson, Philip; Pennell, Craig; Martin, N.G.; Evans, D.M.; Hinds, D.A.; Hopper, J.L.

In: Journal of Allergy and Clinical Immunology, Vol. 133, No. 6, 06.2014, p. 1564-1571.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype

AU - Ferreira, M.A.R.

AU - Matheson, M.C.

AU - Tang, C.S.

AU - Granell, R.

AU - Ang, Wei

AU - Hui, Jennie

AU - Kiefer, A.K.

AU - Duffy, D.L.

AU - Baltic, S.

AU - Danoy, P.

AU - Bui, M.

AU - Price, L.

AU - Sly, P.D.

AU - Eriksson, N.

AU - Madden, P.A.

AU - Abramson, M.J.

AU - Holt, Patrick

AU - Heath, A.C.

AU - Hunter, Michael

AU - Musk, Arthur

AU - Robertson, C.F.

AU - Le Souëf, Peter

AU - Montgomery, G.W.

AU - Henderson, A.J.

AU - Tung, J.Y.

AU - Dharmage, S.C.

AU - Brown, M.A.

AU - James, Alan

AU - Thompson, Philip

AU - Pennell, Craig

AU - Martin, N.G.

AU - Evans, D.M.

AU - Hinds, D.A.

AU - Hopper, J.L.

PY - 2014/6

Y1 - 2014/6

N2 - 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.

AB - 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.

U2 - 10.1016/j.jaci.2013.10.030

DO - 10.1016/j.jaci.2013.10.030

M3 - Article

VL - 133

SP - 1564

EP - 1571

JO - The Journal of Allergy and Clinical Immunology

JF - The Journal of Allergy and Clinical Immunology

SN - 0091-6749

IS - 6

ER -