荟萃分析确定了 29 个额外的溃疡性结肠炎风险位点，使已确认的关联数量增加到 47 个。
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
机构信息
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
出版信息
Nat Genet. 2011 Mar;43(3):246-52. doi: 10.1038/ng.764. Epub 2011 Feb 6.
Abstract
Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10(-8)), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.
摘要
全基因组关联研究和候选基因研究已经确定了溃疡性结肠炎的 18 个易感性位点。我们对六个溃疡性结肠炎全基因组关联研究数据集进行了荟萃分析，包含 6687 例病例和 19718 例对照，并且在 9628 例病例和 12917 例对照中对顶级关联信号进行了随访。我们发现了 29 个额外的风险位点（P < 5 × 10(-8)），将溃疡性结肠炎相关的位点数量增加到 47 个。在使用 GRAIL 注释相关区域、表达数量性状基因座数据以及与非同义 SNP 的相关性后，我们鉴定了许多候选基因，这些基因可能为疾病发病机制提供了重要的见解，包括 IL1R2、IL8RA-IL8RB、IL7R、IL12B、DAP、PRDM1、JAK2、IRF5、GNA12 和 LSP1。目前已确认的炎症性肠病风险位点总数为 99 个，其中包括克罗恩病和溃疡性结肠炎之间至少 28 个共享的关联信号。
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Pathol Res Pract. 2010 Sep 15;206(9):616-24. doi: 10.1016/j.prp.2010.05.004. Epub 2010 Jul 13.
2
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3
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