Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE Network.
Genetic variants associated with the white blood cell count in 13,923 subjects in the eMERGE Network.
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DOI：
10.1007/s00439-011-1103-9
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发表时间：
2012-04
期刊：
影响因子：
5.3
通讯作者：
Electronic Medical Records and Genomics (eMERGE) Network
中科院分区：
文献类型：
--
作者：
Crosslin DR;McDavid A;Weston N;Nelson SC;Zheng X;Hart E;de Andrade M;Kullo IJ;McCarty CA;Doheny KF;Pugh E;Kho A;Hayes MG;Pretel S;Saip A;Ritchie MD;Crawford DC;Crane PK;Newton K;Li R;Mirel DB;Crenshaw A;Larson EB;Carlson CS;Jarvik GP;Electronic Medical Records and Genomics (eMERGE) Network
白色血细胞计数（WBC）在已确定的慢性疾病炎症预测因子中是独特的，因为它在常规患者护理过程中对无症状患者进行常规测量。我们领导了一项全基因组关联分析，以确定电子病历和基因组学（eMERGE）网络中13，923名受试者中与WBC水平相关的变异。我们确定了两个感兴趣的区域，每个区域都是非洲大陆（AA）或欧洲大陆（EA）遗传决定祖先的主题所独有的。WBC在不同的祖先群体之间存在差异。尽管是特定的祖先，这些地区是可识别的综合分析。在AA受试者中，1 q21上Duffy抗原/趋化因子受体基因（DARC）周围的区域表现出显著的相关性（p值= 6.71e-55）。这些结果验证了先前报道的WBC与启动子区调控变体rs 2814778之间的关联，该关联导致Duffy阴性表型（Fy-/-）。第二个错义变体（rs 12075）负责达菲血型系统的两个主要抗原Fya和Fyb。这两种变体由四个等位基因组成，共同作用产生五种抗原和随后的表型。我们能够确定这两种变体对WBC的边际和新的相互作用效应。在EA受试者中，我们在17 q21区域识别出标记三个独立基因的显著相关SNP：（1）GSDMA，（2）MED 24和（3）PSMD 3。据报道，该区域的变体与WBC、中性粒细胞计数和炎性疾病（包括哮喘和克罗恩病）相关。
White blood cell count (WBC) is unique among identified inflammatory predictors of chronic disease in that it is routinely measured in asymptomatic patients in the course of routine patient care. We led a genome-wide association analysis to identify variants associated with WBC levels in 13,923 subjects in the electronic Medical Records and Genomics (eMERGE) Network. We identified two regions of interest that were each unique to subjects of genetically determined ancestry to the African continent (AA) or to the European continent (EA). WBC varies among different ancestry groups. Despite being ancestry specific, these regions were identifiable in the combined analysis. In AA subjects, the region surrounding the Duffy antigen/chemokine receptor gene (DARC) on 1q21 exhibited significant association (p value = 6.71e–55). These results validate the previously reported association between WBC and of the regulatory variant rs2814778 in the promoter region, which causes the Duffy negative phenotype (Fy−/−). A second missense variant (rs12075) is responsible for the two principal antigens, Fya and Fyb of the Duffy blood group system. The two variants, consisting of four alleles, act in concert to produce five antigens and subsequent phenotypes. We were able to identify the marginal and novel interaction effects of these two variants on WBC. In the EA subjects, we identified significantly associated SNPs tagging three separate genes in the 17q21 region: (1) GSDMA, (2) MED24, and (3) PSMD3. Variants in this region have been reported to be associated with WBC, neutrophil count, and inflammatory diseases including asthma and Crohn’s disease.
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影响因子：
30.8
作者：
Barrett, Jeffrey C.;Clayton, David G.;Concannon, Patrick;Akolkar, Beena;Cooper, Jason D.;Erlich, Henry A.;Julier, Cecile;Morahan, Grant;Nerup, Jorn;Nierras, Concepcion;Plagnol, Vincent;Pociot, Flemming;Schuilenburg, Helen;Smyth, Deborah J.;Stevens, Helen;Todd, John A.;Walker, Neil M.;Rich, Stephen S.
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影响因子：
64.8
作者：
Breslow, David K.;Collins, Sean R.;Bodenmiller, Bernd;Aebersold, Ruedi;Simons, Kai;Shevchenko, Andrej;Ejsing, Christer S.;Weissman, Jonathan S.
通讯作者：
Weissman, Jonathan S.
影响因子：
9.8
作者：
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通讯作者：
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