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

被引：166

作者：

Ferreira, Manuel A. R. ^{[1
]}

Matheson, Melanie C. ^{[2
]}

Tang, Clara S. ^{[1
,3
,4
]}

Granell, Raquel ^{[5
]}

Ang, Wei ^{[6
]}

Hui, Jennie ^{[7
,8
,9
,10
]}

Kiefer, Amy K. ^{[11
]}

Duffy, David L. ^{[1
]}

Baltic, Svetlana ^{[12
,13
]}

Danoy, Patrick ^{[14
]}

Bui, Minh ^{[2
]}

Price, Loren ^{[12
,13
]}

Sly, Peter D. ^{[15
]}

Eriksson, Nicholas ^{[11
]}

Madden, Pamela A. ^{[16
]}

Abramson, Michael J. ^{[17
]}

Holt, Patrick G. ^{[18
]}

Heath, Andrew C. ^{[16
]}

Hunter, Michael ^{[8
,10
]}

Musk, Bill ^{[10
,19
,20
]}

Robertson, Colin F. ^{[21
]}

Le Souef, Peter ^{[22
]}

Montgomery, Grant W. ^{[1
]}

Henderson, A. John ^{[5
]}

Tung, Joyce Y. ^{[11
]}

Dharmage, Shyamali C. ^{[2
]}

Brown, Matthew A. ^{[14
]}

James, Alan ^{[10
,19
,23
]}

Thompson, Philip J. ^{[12
,13
]}

Pennell, Craig ^{[6
]}

Martin, Nicholas G. ^{[1
]}

Evans, David M. ^{[5
,24
]}

Hinds, David A. ^{[11
]}

Hopper, John L. ^{[2
]}

机构：

[1] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia

[2] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia

[3] Univ Hong Kong, Ctr Genom Sci, Dept Psychiat, Hong Kong, Hong Kong, Peoples R China

[4] Univ Hong Kong, Ctr Genom Sci, Dept Surg & Med, Hong Kong, Hong Kong, Peoples R China

[5] Univ Bristol, Sch Social & Community Med, Bristol BS8 1TH, Avon, England

[6] Univ Western Australia, Sch Womens & Infants Hlth, Subiaco, WA, Australia

[7] PathWest Lab Med Western Australia, Nedlands, WA, Australia

[8] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia

[9] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia

[10] Sir Charles Gairdner Hosp, Bussel Populat Med Res Fdn, Perth, WA, Australia

[11] 23&Me, Mountain View, CA USA

[12] Univ Western Australia, Lung Inst Western Australia, Perth, WA 6009, Australia

[13] Univ Western Australia, Ctr Asthma Allergy & Resp Res, Perth, WA 6009, Australia

[14] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia

[15] Royal Childrens Hosp, Queensland Childrens Med Res Inst, Brisbane, Qld, Australia

[16] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63130 USA

[17] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic, Australia

[18] Univ Western Australia, Telethon Inst Child Hlth Res, Subiaco, WA, Australia

[19] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia

[20] Sir Charles Gairdner Hosp, Dept Resp Med, Perth, WA, Australia

[21] Murdoch Childrens Res Inst, Melbourne, Vic, Australia

[22] Princess Margaret Hosp Children, Sch Paediat & Child Hlth, Perth, WA, Australia

[23] West Australian Sleep Disorders Res Inst, Dept Pulm Physiol, Nedlands, WA, Australia

[24] Univ Bristol, Med Res Council MRC Ctr Causal Anal Translat Epid, Bristol BS8 1TH, Avon, England

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2014年 / 133卷 / 06期

基金：

澳大利亚研究理事会; 美国国家卫生研究院; 加拿大健康研究院; 英国医学研究理事会;

关键词：

Rhinitis; atopy; selection; genetic correlation; bivariate; single nucleotide polymorphism; GENE-EXPRESSION; SUSCEPTIBILITY LOCI; MULTIPLE-SCLEROSIS; POPULATION STRATIFICATION; TRANSCRIPTION FACTORS; JAPANESE POPULATION; ALLERGIC RHINITIS; METAANALYSIS; DISEASE; SP1;

D O I：

10.1016/j.jaci.2013.10.030

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

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 x 10(-9)) and CLEC16A (rs62026376; OR, 1.17; P = 1 x 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 x 10(-7)) and rs76043829 in TNS1 (OR, 1.23; P = 2 x 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.

引用

页码：1564 / 1571

页数：8

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