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五个新的与早发性炎症性肠病相关的常见变异位点。

Common variants at five new loci associated with early-onset inflammatory bowel disease.

机构信息

Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.

出版信息

Nat Genet. 2009 Dec;41(12):1335-40. doi: 10.1038/ng.489. Epub 2009 Nov 15.

Abstract

The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

摘要

炎症性肠病(IBD)中的克罗恩病和溃疡性结肠炎是西方世界儿童和青年人群中发病率较高的常见疾病。在这里,我们报告了一项涉及 3426 名发病早的 IBD 患者和 11963 名通过欧洲和北美国际合作进行基因匹配的对照者的全基因组关联研究结果,该研究结果扩展了之前一项涉及 1011 名发病早的 IBD 患者的研究结果。我们已经确定了与早发性 IBD 易感性相关的五个新区域,包括位于细胞因子基因 IL27 附近的 16p11(rs8049439,P=2.41×10(-9))、22q12(rs2412973,P=1.55×10(-9))、10q22(rs1250550,P=5.63×10(-9))、2q37(rs4676410,P=3.64×10(-8))和 19q13.11(rs10500264,P=4.26×10(-10))。我们的扫描还在 32 个先前与成人发病的克罗恩病相关的位点中的 23 个位点和 17 个与成人发病的溃疡性结肠炎相关的位点中的 8 个位点检测到了关联,突出了早发和成人发病的 IBD 之间密切的发病机制关系。

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