Inflammatory bowel disease (IBD) is a common inflammatory disorder with complex etiology that involves both genetic and environmental triggers, including but not limited to defects in bacterial clearance, defective mucosal barrier and persistent dysregulation of the immune response to commensal intestinal bacteria. IBD is characterized by two distinct phenotypes: Crohn’s disease (CD) and ulcerative colitis (UC). Previously reported GWA studies have identified genetic variation accounting for a small portion of the overall genetic susceptibility to CD and an even smaller contribution to UC pathogenesis. We hypothesized that stratification of IBD by age of onset might identify additional genes associated with IBD. To that end, we carried out a GWA analysis in a cohort of 1,011 individuals with pediatric-onset IBD and 4,250 matched controls. We identified and replicated significantly associated, previously unreported loci on chromosomes 20q13 (rs2315008[T] and rs4809330[A]; P = 6.30 × 10−8 and 6.95 × 10−8, respectively; odds ratio (OR) = 0.74 for both) and 21q22 (rs2836878[A]; P = 6.01 × 10−8; OR = 0.73), located close to the TNFRSF6B and PSMG1 genes, respectively.
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机译：炎性肠病（IBD）是一种病因复杂的常见炎性疾病，涉及遗传和环境触发因素，包括但不限于细菌清除缺陷，黏膜屏障缺陷和对共肠细菌免疫反应的持续失调。 IBD的特征在于两种不同的表型：克罗恩病（CD）和溃疡性结肠炎（UC）。先前报道的GWA研究已经发现遗传变异占CD总体遗传易感性的一小部分，而对UC发病机理的贡献甚至更小。我们假设按发病年龄对IBD进行分层可确定与IBD相关的其他基因。为此，我们对1,011名患儿IBD的患者和4,250名相匹配的对照组进行了GWA分析。我们在染色体20q13上鉴定并复制了显着相关的，以前未报告的基因座（rs2315008 [T]和rs4809330 [A]； P = 6.30×10 -8 和6.95×10 -8 分别；比值比（OR）均为0.74）和21q22（rs2836878 [A]； P = 6.01×10 -8 ； OR = 0.73），位于TNFRSF6B和PSMG1基因附近， 分别。
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