Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Nat Genet. 2010 Apr;42(4):295-302. doi: 10.1038/ng.543. Epub 2010 Feb 28.
We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P(GWAS) < 10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (P(combined) < 5 x 10(-8)); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection. There was evidence to suggest associations for a further 13 regions. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P < 0.0028, FDR 5%) with cis gene expression.
我们对 4533 名乳糜泻患者（病例）和 10750 名对照进行了第二代全基因组关联研究。我们对 113 个经过 P(GWAS) < 10(-4) 筛选的 SNP 进行了基因分型，并在另外 4918 个病例和 5684 个对照中对 14 个已知基因座的 18 个 SNP 进行了基因分型。来自 13 个新区域的变异达到了全基因组显著水平（P(combined) < 5 x 10(-8)）；大多数包含具有免疫功能的基因（BACH2、CCR4、CD80、CIITA-SOCS1-CLEC16A、ICOSLG 和 ZMIZ1），ETS1、RUNX3、THEMIS 和 TNFRSF14 在胸腺 T 细胞选择中具有关键作用。还有证据表明，另外 13 个区域存在关联。在对 1469 个全血样本进行的表达数量性状基因座元分析中，38 个测试基因座中有 20 个（52.6%）乳糜泻风险变异与顺式基因表达相关（P < 0.0028，FDR 为 5%）。
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