Genome-wide association identifies multiple ulcerative colitis susceptibility loci.
Genome-wide association identifies multiple ulcerative colitis susceptibility loci.
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溃疡性结肠炎（UC）是一种胃肠道的慢性复发性炎症疾病，其病因涉及复杂的遗传和环境因素。我们进行了两项不同的UC全基因组关联（GWA）研究，并与先前发表的一项扫描结果共同分析，总共包括2693例UC患者和6791例对照。来自14个独立位点的总共59个单核苷酸多态性（SNP）达到P < 10⁻⁵。其中7个位点超过了全基因组显著性水平（P < 5×10⁻⁸）。在对另外一组2009例UC患者和1580例对照进行检测后，14个位点显著相关，包括FCGR2A、5p15、2p16、CARD9和ORMDL3与UC的新型关联。在我们的研究中，我们证实了与14个先前确定的UC易感位点的关联，同时对已知的克罗恩病（CD）位点的分析表明，大约一半已知的CD关联与UC共享。这些数据表明约30个位点与UC相关，为疾病发病机制提供了新的见解。
Ulcerative colitis (UC) is a chronic, relapsing inflammatory condition of the gastrointestinal tract with a complex genetic and environmental etiology. We performed two distinct UC genome-wide association (GWA) studies, and analyzed these jointly with a previously published scan, comprising, in aggregate, 2,693 patients with UC and 6,791 controls. A total of 59 SNPs from 14 independent loci attained P < 10−5. Seven of these loci exceeded genome-wide significance (P < 5 × 10−8). After testing an independent cohort of 2009 patients with UC and 1580 controls, 14 loci were significantly associated, including novel UC associations with FCGR2A, 5p15, 2p16, CARD9 and ORMDL3. In our study we confirmed association with 14 previously identified UC susceptibility loci, while an analysis of acknowledged Crohn's disease (CD) loci showed that roughly half of known CD associations are shared with UC. These data implicate approximately 30 loci for UC, providing novel insights into disease pathogenesis.