Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.
Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype.
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DOI：
10.1016/j.jaci.2013.10.030
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发表时间：
2014-06
影响因子：
14.2
通讯作者：
Hopper, John L.
中科院分区：
文献类型：
--
作者：
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 Souef, 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.
迄今为止，没有全基因组关联研究（GWAS）考虑到哮喘与花粉热的联合表型。先前对塔斯马尼亚纵向健康研究的家庭数据的分析提供了证据，表明这种表型比没有花粉热的哮喘具有更强的遗传原因。我们试图对哮喘和花粉热进行GWAS，以确定与这两种疾病相关的变异。我们对GWASs进行了荟萃分析，比较了医生诊断为哮喘和花粉热的患者（n = 6,685）和没有疾病的患者（n = 14,091）。在全基因组意义上，我们发现了11个与哮喘合并花粉热风险相关的独立变异，其中2个与过敏性疾病的关联首次达到这种显著水平：ZBTB10 （rs7009110；比值比[OR]， 1.14; P = 4 × 10−9）和CLEC16A （rs62026376； OR, 1.17; P = 1 × 10−8）。与哮喘和花粉热风险增加相关的rs62026376:C等位基因也被发现与单核细胞中附近DEXI基因的表达减少有关。这11种变异分别与哮喘和花粉热的风险相关，但与个体表型的估计关联要弱于哮喘与花粉热表型的联合关联。lrrrc32附近的变异是花粉热比哮喘更强的危险因素，而GSDMA和TSLP附近的变异则相反。与哮喘和花粉热风险相关的单核苷酸多态性包括IL2RA附近的rs41295115 （OR, 1.28; P = 5 × 10−7）和TNS1附近的rs76043829 （OR, 1.23; P = 2 × 10−6）。通过关注哮喘与花粉热的联合表型，可以更有效地识别与过敏性疾病风险相关的变异。
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. We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. 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). 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). 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.
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影响因子：
168.9
作者：
Ferreira, Manuel A. R.;Matheson, Melanie C.;Duffy, David L.;Marks, Guy B.;Hui, Jennie;Le Souef, Peter;Danoy, Patrick;Baltic, Svetlana;Nyholt, Dale R.;Jenkins, Mark;Hayden, Catherine;Willemsen, Gonneke;Ang, Wei;Kuokkanen, Mikko;Beilby, John;Cheah, Faang;de Geus, Eco J. C.;Ramasamy, Adaikalavan;Vedantam, Sailaja;Salomaa, Veikko;Madden, Pamela A.;Heath, Andrew C.;Hopper, John L.;Visscher, Peter M.;Musk, Bill;Leeder, Stephen R.;Jarvelin, Marjo-Riitta;Pennell, Craig;Boomsma, Dorret I.;Hirschhorn, Joel N.;Walters, Haydn;Martin, Nicholas G.;James, Alan;Jones, Graham;Abramson, Michael J.;Robertson, Colin F.;Dharmage, Shyamali C.;Brown, Matthew A.;Montgomery, Grant W.;Thompson, Philip J.
通讯作者：
Thompson, Philip J.
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
30.8
作者：
Fairfax, Benjamin P.;Makino, Seiko;Radhakrishnan, Jayachandran;Plant, Katharine;Leslie, Stephen;Dilthey, Alexander;Ellis, Peter;Langford, Cordelia;Vannberg, Fredrik O.;Knight, Julian C.
通讯作者：
Knight, Julian C.
影响因子：
30.8
作者：
通讯作者：
--
DOI：
10.1056/nejmoa0908547
发表时间：
2010-05-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Jin Y;Birlea SA;Fain PR;Gowan K;Riccardi SL;Holland PJ;Mailloux CM;Sufit AJ;Hutton SM;Amadi-Myers A;Bennett DC;Wallace MR;McCormack WT;Kemp EH;Gawkrodger DJ;Weetman AP;Picardo M;Leone G;Taïeb A;Jouary T;Ezzedine K;van Geel N;Lambert J;Overbeck A;Spritz RA
通讯作者：
Spritz RA