多种常见的乳糜泻易感基因变异影响免疫基因表达。

Multiple common variants for celiac disease influencing immune gene expression.

机构信息

Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

出版信息

Nat Genet. 2010 Apr;42(4):295-302. doi: 10.1038/ng.543. Epub 2010 Feb 28.

DOI:10.1038/ng.543

PMID:20190752

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2847618/

Abstract

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.

摘要

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%）。