A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study.
A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study.
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DOI：
10.1016/j.jaci.2011.09.029
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
O'Connor GT
中科院分区：
文献类型：
--
作者：
Granada M;Wilk JB;Tuzova M;Strachan DP;Weidinger S;Albrecht E;Gieger C;Heinrich J;Himes BE;Hunninghake GM;Celedón JC;Weiss ST;Cruikshank WW;Farrer LA;Center DM;O'Connor GT
特应性和血浆IgE浓度是基因复杂的性状，导致IgE失调和临床特应性的特定遗传风险因素是一个活跃的研究领域。
为了确定导致IgE失调的遗传风险因素，对来自弗雷明汉心脏研究（FHS）的6819名参与者进行了一项全基因组关联研究（GWAS）。根据p值和相邻SNP之间的连锁不平衡选择了70个排名靠前的SNP，并在与来自KORA、B58C和CAMP队列的5个独立人群的荟萃分析中进行了评估。
位于FCER1A、STAT6和IL - 13三个基因区域的13个SNP在FHS的GWAS中被发现具有全基因组显著性。这三个区域中最显著的SNP分别是rs2251746（FCER1A，p值2.11×10⁻¹²）、rs1059513（STAT6，p值2.87×10⁻⁸）和rs1295686（IL - 13，p值3.55×10⁻⁸）。在结合FHS和复制队列的荟萃分析中，另外四个基因区域——HLA - G、HLA - DQA2、HLA - A和DARC——达到了全基因组统计学意义，尽管DARC的关联似乎不独立于附近FCER1A基因中的SNP。
FHS的这项GWAS已经确定了HLA基因中的基因位点，这些位点可能在IgE失调和特应性的发病机制中起作用。它还证实了已知的易感位点FCER1A、STAT6和IL - 13与总IgE失调的关联。
Atopy and plasma IgE concentration are genetically complex traits, and the specific genetic risk factors that lead to IgE dysregulation and clinical atopy are an area of active investigation. To ascertain the genetic risk factors which lead to IgE dysregulation. A genome wide association study (GWAS) was performed in 6,819 participants from the Framingham Heart Study (FHS). Seventy of the top SNPs were selected based on p-values and linkage disequilibrium among neighboring SNPs and evaluated in a meta-analysis with five independent populations from the KORA, B58C, and CAMP cohorts. Thirteen SNPs located in the region of three genes, FCER1A, STAT6, and IL-13, were found to have genome-wide significance in the FHS GWAS. The most significant SNPs from the three regions were rs2251746 (FCER1A, p-value 2.11×10-12), rs1059513 (STAT6, p-value 2.87×10-08), and rs1295686 (IL-13, p-value 3.55×10-08). Four additional gene regions - HLA-G, HLA-DQA2, HLA-A, and DARC - reached genome-wide statistical significance in meta-analysis combining FHS and replication cohorts, although the DARC association did not appear independent of SNPs in the nearby FCER1A gene. This GWAS of the FHS has identified genetic loci in HLA genes that may have a role in the pathogenesis of IgE dysregulation and atopy. It also confirmed the association of known susceptibility loci, FCER1A, STAT6, and IL-13, for the dysregulation of total IgE.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
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.
通讯作者：
Rich, Stephen S.
影响因子：
32.4
作者：
Lee, GR;Fields, PE;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
56.9
作者：
LEVINE, BB;STEMBER, RH;FOTINO, M
通讯作者：
FOTINO, M
DOI：
10.1073/pnas.76.6.2903
发表时间：
1979-01-01
影响因子：
11.1
作者：
MARSH, DG;CHASE, GA;BIAS, WB
通讯作者：
BIAS, WB